ES2368334T3

ES2368334T3 - N-PHENYLARSULFONAMIDE COMPOSITE, PHARMACEUTICAL COMPOSITION THAT UNDERSTANDS THE COMPOUND AS AN ACTIVE PRINCIPLE, SYNTHETIC INTERMEDIATE FOR THE COMPOUND AND PROCEDURES FOR THE PREPARATION.

Info

Publication number: ES2368334T3
Application number: ES05109059T
Authority: ES
Inventors: Atsushi Naganawa; Tetsuji Saitoh; Kaoru Kobayashi; Takayuki Maruyama; Yoshihiko Nakai; Shinsuke Hashimoto
Original assignee: Ono Pharmaceutical Co Ltd
Current assignee: Ono Pharmaceutical Co Ltd
Priority date: 2001-03-12
Filing date: 2002-03-11
Publication date: 2011-11-16
Anticipated expiration: 2022-03-11

Abstract

Un compuesto de N-fenilarilsulfonilamida de fórmula (I) **Fórmula** en la que R1 es COOH, 5-tetrazolilo, o 5-oxo-1,2,4-oxadiazolilo; R2 es hidrógeno, metilo, metoxi o cloro; R3 y R4 son una combinación de (1) metilo y metilo, (2) metil y cloro, o (3) cloro y metilo; o R3 y R4 se toman junto con el carbono al que R3 y R4 están unidos para formar un anillo ciclopenteno, ciclohexeno o benceno; R5 es isopropilo, isobutilo, 2-metil-2-propenilo, ciclopropilmetilo, etilo, propilo, 2-propenilo o 2-hidroxi-10 2- metilpropilo; Ar es piridilo, 5-metil-2-furilo o tiazolilo opcionalmente sustituido con metilo; y n es cero o 1 y cuando R1 es 5- tetrazolilo o 5-oxo-1,2,4-oxadiazolilo, n es cero, un alquil éster del mismo o una sal no tóxica del mismo, con la condición de que se excluya ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, un alquil éster del mismo o una sal no tóxica del mismo.An N-phenylethylsulfonylamide compound of formula (I) ** Formula ** in which R 1 is COOH, 5-tetrazolyl, or 5-oxo-1,2,4-oxadiazolyl; R2 is hydrogen, methyl, methoxy or chlorine; R3 and R4 are a combination of (1) methyl and methyl, (2) methyl and chlorine, or (3) chlorine and methyl; or R3 and R4 are taken together with the carbon to which R3 and R4 are attached to form a cyclopentene, cyclohexene or benzene ring; R5 is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl, ethyl, propyl, 2-propenyl or 2-hydroxy-10-methylpropyl; Ar is pyridyl, 5-methyl-2-furyl or thiazolyl optionally substituted with methyl; and n is zero or 1 and when R1 is 5- tetrazolyl or 5-oxo-1,2,4-oxadiazolyl, n is zero, an alkyl ester thereof or a non-toxic salt thereof, with the proviso that acid is excluded 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid alkyl ester thereof or a non-toxic salt thereof.

Description

Compuesto de N-fenilarilsulfonamida, composición farmacéutica que comprende el compuesto como principio activo, intermedio sintético para el compuesto y procedimientos para su preparación 5 N-phenylarylsulfonamide compound, pharmaceutical composition comprising the compound as active ingredient, synthetic intermediate for the compound and processes for its preparation.

Field of the Invention

La presente invención se refiere a un compuesto de N-fenilarilsulfonamida. 10 De forma más detallada, la presente invención se refiere a The present invention relates to an N-phenylarylsulfonamide compound. 10 In more detail, the present invention relates to

(1) un compuesto de N-fenilarilsulfonamida de fórmula (I) (1) an N-phenylarylsulfonamide compound of formula (I)

en la que todos los símbolos tienen los mismos significados que se definen más adelante en el presente 15 documento, in which all symbols have the same meanings that are defined later in this document,

(2) un antagonista del receptor de prostaglandina E2 (EP1) que comprende el compuesto como un ingrediente activo. (2) a prostaglandin E2 receptor antagonist (EP1) comprising the compound as an active ingredient.

Background Technique

20 La prostaglandina E2 (abreviada como PGE2) se conoce como un metabolito de la cascada del araquidonato. También se sabe que la PGE2 posee una actividad citoprotectora, una actividad de contracción del útero, un efecto de inducción de dolor, un efecto promotor de la peristalsis digestiva, un efecto promotor de la vigilia, un efecto supresor sobre la secreción de ácido gástrico, un efecto hipotensor, una actividad diurética y similares. 20 Prostaglandin E2 (abbreviated as PGE2) is known as a metabolite of the arachidonate cascade. It is also known that PGE2 has a cytoprotective activity, a contraction activity of the uterus, a pain induction effect, a promoter effect of digestive peristalsis, a promoter effect of wakefulness, a suppressive effect on gastric acid secretion, a hypotensive effect, a diuretic activity and the like.

25 En un estudio reciente, se descubrió que los receptores de PGE2 se dividen en algunos subtipos que poseen diferentes papeles físicos. En el momento actual se conocen cuatro subtipos de receptores y se denominan EP1, EP2, EP3 y EP4 respectivamente (Negishi M et al., J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)). 25 In a recent study, it was discovered that PGE2 receptors are divided into some subtypes that have different physical roles. At present, four receptor subtypes are known and are called EP1, EP2, EP3 and EP4 respectively (Negishi M et al., J. Lipid Mediators Cell Signaling, 12, 379-391 (1995)).

30 La PGE2 posee una diversidad de actividades fisiológicas, de forma que una acción indeseada distinta de la buscada se considera un efecto secundario. Se han investigado el papel de cada subtipo de receptor y compuestos que sólo muestran efecto sobre subtipos específicos para solucionar dicho problema. 30 PGE2 has a variety of physiological activities, so that an unwanted action other than the one sought is considered a side effect. The role of each receptor subtype and compounds that only show effect on specific subtypes to solve this problem have been investigated.

Entre estos subtipos, se sabe que el subtipo EP1 está relacionado con la inducción de dolor, pirexia (inducción de Among these subtypes, it is known that the EP1 subtype is related to pain induction, pyrexia (induction of

35 fiebre) y diuresis (ref Br. J Pharmacol., 112, 735 740 (1994); European J. Pharmacol., 152 273-279 (1988); Gen Pharmacol, Sep. 1992, 23 805-809). Por lo tanto, los compuestos que antagonizan este receptor se consideran útiles como analgésicos, como agentes antipiréticos y como agentes para tratar la polaquiuria (micción frecuente). 35 fever) and diuresis (ref Br. J Pharmacol., 112, 735 740 (1994); European J. Pharmacol., 152 273-279 (1988); Gen Pharmacol, Sep. 1992, 23 805-809). Therefore, the compounds that antagonize this receptor are considered useful as analgesics, as antipyretic agents and as agents for treating polaquiuria (frequent urination).

También se sabe que los antagonistas de EP1 poseen un efecto supresor sobre los focos de cripta aberrantes y la 40 formación de pólipos intestinales, y que indican una actividad antitumoral eficaz (ref. documento WO00/69465). It is also known that EP1 antagonists have a suppressive effect on aberrant crypt foci and the formation of intestinal polyps, and that they indicate an effective antitumor activity (ref. WO00 / 69465).

Una vez que los fármacos se han absorbido en el cuerpo, principalmente migran al interior del torrente sanguíneo. Después se transportan a la sangre y se suministran a los órganos diana. Finalmente, ejercen su potencia. Sin embargo, algunos fármacos no ejercen su potencia porque se combinan con algunas proteínas que están contenidas Once the drugs have been absorbed into the body, they mainly migrate into the bloodstream. They are then transported to the blood and supplied to the target organs. Finally, they exert their power. However, some drugs do not exert their potency because they are combined with some proteins that are contained.

45 en la sangre como sustancias nutritivas. Aunque algunos compuestos son eficaces en experimentos in vitro, con frecuencia puede ocurrir que no sean eficaces en experimentos in vivo. Y es bien sabido que no hay una relación específica estructura-actividad sobre la unión entre fármacos y proteínas, y que es muy difícil descubrir la generalidad. 45 in the blood as nutrients. Although some compounds are effective in in vitro experiments, they may often not be effective in in vivo experiments. And it is well known that there is no specific structure-activity relationship on the union between drugs and proteins, and that it is very difficult to discover generality.

50 Los presentes inventores encontraron un compuesto útil que es un antagonista de EP1, y presentaron una solicitud de patente. En la memoria descriptiva del documento WO98/27053 (documento EP947500), se desvela que un compuesto de sulfonamida de fórmula (A) en la que los grupos The present inventors found a useful compound that is an EP1 antagonist, and filed a patent application. In the specification of WO98 / 27053 (EP947500), it is disclosed that a sulfonamide compound of formula (A) in which the groups

5 son, cada uno, independientemente, un anillo carbocíclico C5-15 etc.; Z1A es COR1 etc.; Z2A es hidrógeno etc.; R1A es hidroxi etc.; Z3A es un enlace sencillo etc.; Z4A es SO2 etc.; Z5A es un anillo heterocíclico de 5 a 7 miembros que contiene uno o dos átomos de oxígeno, azufre o nitrógeno, que puede estar sustituido con 1 a 5 R5A etc.; R5A (si hay 5 are each independently a C5-15 carbocyclic ring etc .; Z1A is COR1 etc .; Z2A is hydrogen etc .; R1A is hydroxy etc .; Z3A is a simple link etc .; Z4A is SO2 etc .; Z5A is a 5- to 7-membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atoms, which may be substituted with 1 to 5 R5A etc .; R5A (if there is

10 dos o más R5A, cada uno independiente) es hidrógeno, alquilo C1-6, etc.; R2A es Z7A-alquileno C1-4 etc.; Z7A es oxígeno etc.; R3A es trifluorometilo etc.; R4A es alquilo C1-8 etc.; nA y tA son, cada uno independientemente, 1 a 4 (como extracto), 10 two or more R5A, each independent) is hydrogen, C1-6 alkyl, etc .; R2A is Z7A-C1-4 alkylene etc .; Z7A is oxygen etc .; R3A is trifluoromethyl etc .; R4A is C1-8 alkyl etc .; nA and tA are each independently 1 to 4 (as an extract),

se une a un receptor de PGE2, especialmente al receptor EP1, mostrando una actividad agonista o antagonista. La binds to a PGE2 receptor, especially the EP1 receptor, showing agonist or antagonistic activity. The

15 memoria descriptiva desveló que el compuesto que tiene actividad antagonista es útil para la prevención de abortos, como un analgésico, como un antidiarreico, como un agente hipnagógico y para tratar la polaquiuria (micción frecuente), mientras que el que tiene actividad agonista es útil para inducir abortos, como un abstergente, como un agente anti-úlceras, como un agente anti-gastritis, como un agente antihipertensivo y como un agente diurético. 15 Descriptive report revealed that the compound that has antagonistic activity is useful for the prevention of abortions, as an analgesic, as an antidiarrheal, as a hypnagogic agent and to treat polaquiuria (frequent urination), while the one with agonist activity is useful to induce abortions, as an abstergent, as an anti-ulcer agent, as an anti-gastritis agent, as an antihypertensive agent and as a diuretic agent.

20 En la presente solicitud de patente, por ejemplo, los siguientes compuestos se describen de forma específica. In the present patent application, for example, the following compounds are specifically described.

(1)(one): Ejemplo 18(93) Example 18 (93)

(2)(2): Ejemplo 18(113) Example 18 (113)

(3)(3): Ejemplo 18(125) Example 18 (125)

(4) Ejemplo 18(121) (4) Example 18 (121)

(5)(5): Ejemplo 18(126) Example 18 (126)

5 (6) Ejemplo 18(59) 5 (6) Example 18 (59)

(7)(7): Ejemplo 18(124) Example 18 (124)

(8)(8): Ejemplo 18(94) Example 18 (94)

(9)(9): Ejemplo 21 (13) Example 21 (13)

(10)(10): Ejemplo 21(14) Example 21 (14)

10 En el procedimiento de las investigaciones acerca de estos compuestos, se ha revelado que estos compuestos tienen algunos problemas como que son susceptibles a la influencia de enlace a proteína y que no tienen una actividad in vivo satisfactoria. In the process of investigations of these compounds, it has been revealed that these compounds have some problems such as that they are susceptible to the influence of protein binding and that they do not have satisfactory in vivo activity.

5 Disclosure of the Invention

Como resultado de una investigación enérgica para encontrar aquellos compuestos que se unen de forma selectiva a receptor de subtipo EP1 y tienen una actividad in vivo satisfactoria debido a que se ven menos afectados por el enlace a proteína, los inventores de la presente invención han descubierto que el único compuesto de NAs a result of vigorous research to find those compounds that selectively bind to EP1 subtype receptor and have satisfactory in vivo activity because they are less affected by protein binding, the inventors of the present invention have discovered that the only compound of N

10 fenilarilsulfonamida de fórmula (1) tiene una actividad in vivo muy fuerte y han completado la presente invención. Phenylarylsulfonamide of formula (1) has a very strong in vivo activity and has completed the present invention.

La presente invención también ha descubierto un nuevo intermedio de fórmula (II) The present invention has also discovered a new intermediate of formula (II)

15 en la que todos los símbolos tienen los mismos significados que se definen más adelante en el presente documento, 15 in which all symbols have the same meanings that are defined later in this document,

que se usa para la preparación del compuesto de fórmula (1) y un procedimiento para la preparación del mismo. which is used for the preparation of the compound of formula (1) and a process for the preparation thereof.

20 Se describen diversos compuestos en la memoria descriptiva del documento WO 98/27053, como se ha indicado anteriormente, pero no se describen compuestos de la presente invención y no existen ni descripción, ni sugerencia en cuando a los problemas anteriores, ni procedimientos para la resolución. Various compounds are described in the specification of WO 98/27053, as indicated above, but no compounds of the present invention are described and there is no description, no suggestion as to the above problems, or procedures for the resolution.

La presente invención se refiere a 25 The present invention relates to

(1) un compuesto de N-fenilarilsulfonilamida de fórmula (I) (1) an N-phenylethylsulfonylamide compound of formula (I)

en la que R1 es COOH, 5-tetrazolilo o 5-oxo-1,2,4-oxadiazolilo; wherein R1 is COOH, 5-tetrazolyl or 5-oxo-1,2,4-oxadiazolyl;

R2 es hidrógeno, metilo, metoxi o cloro; R2 is hydrogen, methyl, methoxy or chlorine;

30 R3 y R4 son una combinación de (1) metilo y metilo, (2) metilo y cloro o (3) cloro y metilo; o R3 y R4 se toman junto con el carbono al que R3 y R4 están unidos para formar ciclopenteno, ciclohexeno o un anillo benceno; R5 es isopropilo, isobutilo, 2-metil-2-propenilo, ciclopropilmetilo, etilo, propilo, 2-propenilo o 2-hidroxi-2-metilpropilo; R3 and R4 are a combination of (1) methyl and methyl, (2) methyl and chlorine or (3) chlorine and methyl; or R3 and R4 are taken together with the carbon to which R3 and R4 are attached to form cyclopentene, cyclohexene or a benzene ring; R5 is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl;

35 Ar es piridilo, 5-metil-2-furilo o tiazolilo opcionalmente sustituido con metilo; y n es cero o 1, y cuando R1 es 5tetrazolilo o 5-oxo-1,2,4-oxadiazolilo, n es cero, un alquil éster de los mismos o una sal no tóxica de los mismos, con la condición de que se excluyan ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5iloximetil]benzoico, un alquil éster del mismo o una sal no tóxica del mismo. Ar is pyridyl, 5-methyl-2-furyl or thiazolyl optionally substituted with methyl; and n is zero or 1, and when R1 is 5-tetrazolyl or 5-oxo-1,2,4-oxadiazolyl, n is zero, an alkyl ester thereof or a non-toxic salt thereof, with the proviso that they are excluded 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, an alkyl ester thereof or a non-toxic salt thereof.

40 También se describe en el presente documento un procedimiento para la preparación del mismo. 40 A procedure for the preparation thereof is also described herein.

(7) un antagonista del receptor de PGE2, receptor de subtipo EP1, que comprende el compuesto de fórmula (I) como un principio activo. (7) a PGE2 receptor antagonist, subtype receptor EP1, which comprises the compound of formula (I) as an active ingredient.

Un compuesto de la fórmula (II) también se describe en el presente documento. A compound of the formula (II) is also described herein.

en la que Ar' es un anillo heterocíclico de 5 a 10 miembros opcionalmente sustituido y R6 es wherein Ar 'is an optionally substituted 5-10 membered heterocyclic ring and R6 is

que es un intermedio para el compuesto de la fórmula (I), y which is an intermediate for the compound of the formula (I), and

Un procedimiento para la preparación del compuesto de fórmula (II), también se describe en el presente documento. A process for the preparation of the compound of formula (II) is also described herein.

Los inventores de la presente invención sintetizaron casi todas las combinaciones de los compuestos de la fórmula The inventors of the present invention synthesized almost all combinations of the compounds of the formula

(I) de la presente invención y confirmaron sus actividades. Y todos los compuestos de la misma se prefieren. (I) of the present invention and confirmed their activities. And all the compounds thereof are preferred.

15 El compuesto o compuestos más preferidos tienen Ar de 5-metil-2-furilo, 2-tiazolilo, 5-metil-2-tiazolilo, 2-piridilo y 3piridilo. The most preferred compound or compounds have 5-methyl-2-furyl, 2-thiazolyl, 5-methyl-2-thiazolyl, 2-pyridyl and 3-pyridyl Ar.

Específicamente, son compuestos preferidos: Specifically, preferred compounds are:

Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)-4-metil-5-clorofenoximetil]benzoico, 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) -4-methyl-5-chlorophenoxymethyl] benzoic acid,

25 Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsofonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsofonil)amino]-4-metil-5-clorofenoximetil]benzoico,Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsofonil)amino]-4-metil-5-clorofenoximetil]benzoico,Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsofonil)amino]-4,5-dimetilfenoximetil]benzoico,Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsofonil)amino]-4,5-dimetilfenoximetil]benzoico,Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsofonil)amino]-4,5-dimetilfenoximetil]benzoico,Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsofonil)amino]-4,5-dimetilfenoximetil]benzoico,25 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsophonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsofonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-chloro-4- [2- [N-isopropyl-N- (5-methyl -2-Furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsofonyl) amino] -4-methyl -5-chlorophenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsophonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methoxy-4 acid - [2- [N-Isopropyl-N- (5-methyl-2-furylsophonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methoxy-4- [2- [N-isobutyl-N- (5 -methyl-2-furylsofonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro -5-methylphenoxymethyl] benzoic acid, 3-chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-chloro-4 acid - [2- [N-Isopropyl-N- (5-methyl-2-furylsophonyl) amino] -4,5-dimethylphenoxymethyl] be nzoic,

35 Ácido 3-metil-4-[2-(N-isobutil-N-(5-metil-2-furilsofonil)amino]-4-cloro-5-metilfenoximetil]cinámico, Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsofonil)amino]-4-metil-5-clorofenoximetil]cinámico,Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsofonil)amino]-4-metil-5-clorofenoximetil]cinámico,Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsofonil)amino]-4,5-dimetilfenoximetil]cinámico,Ácido 3-metil-4-[2-[4-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,Ácido 3-metil-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino-4,5-dimetilfenoximetil]cinámico,Ácido4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida,Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, 35 3-Methyl-4- [2- (N-isobutyl-N- (5-methyl-2-furylsophonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid, 4- [2- [N-isopropyl acid -N- (5-methyl-2-furylsofonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic, 4- [2- [N-isobutyl-N- (5-methyl-2-furylsofonyl) amino] - 4-methyl-5-chlorophenoxymethyl] cinnamic, 4- [2- [N-isopropyl-N- (5-methyl-2-furylsophonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-methyl-4- acid [2- [4-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isopropyl-N- (5- methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino-4,5-dimethylphenoxymethyl ] cinnamic, 4- (2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, N- [4-chloro-5-methyl-2- [2] -methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide, 3-methoxy-4- [2- [N-isobutyl-N- (5- methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic,

45 N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi)fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida,Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,Ácido 4-[7-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-1,2,3,4-tetrahidronaftalen-6-iloximetil]benzoico,Ácido 4-[7-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-1,2,3,4-tetrahidronaftalen-6-iloximetil]benzoico, N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, 45 N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy) phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide, N- [4,5 -dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide, N- [4-chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide, N- [4-chloro-5-methyl-2- [4- (5-oxo-1 , 2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide, N- [4-chloro-5-methyl-2- [4- (5- oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide, 4- [6- [N-isobutyl-N- (5- methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4 - [7- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid, 4- [7- [N-isopropyl- N- (5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid, N- [4,5-dimethyl-2- [2-methyl-4- (5 -oxo-1,2,4-oxadiazol-3-yl) phenylm ethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide,

55 N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, 55 N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl- 2-furyl) sulfonylamide, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide, N- [4, 5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide,

N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2furil)sulfonilamida, Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[2-[N-(2-metil-2-propenil)-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-2-naftiloximetil]benzoico, Ácido 3-metil-4-[6-[-N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico, Alcohol 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbencílico, Ácido 4-[6-[N-etil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico, Ácido 4-[6-[N-metil-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-etil-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-(5-metil-2-furilsofonil)-N-propilamino]indan-5-iloximetil]cinámico, Ácido 4-[4,5-dimetil-2-[N-(2-metil-2-propenil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[6-[N-(5-metil-2-furilsofonil)N-(2-metil-2-propenil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-(5-metil-2-furilsofonil)-N-(2-propenil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-propilamino]indan-5-iloximetil]benzoico, Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]benzoico, Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]benzoico, Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-propilamino]fenoximetil]benzoico, Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsofonil)amino]naftalen-2-iloximetil]-3-metilbenzoico, Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsofonil)amino]naftalen-2-iloximetil]-3-metilbenzoico, Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsofonil)amino]naftalen-2-iloximetil]cinámico, Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico, Ácido 3-metil-4-[3-[N-isopropil-N-(5-metil-2-furilsofonil)amino]naftalen-2-iloximetil]cinámico, Ácido 3-metil-4-[3-[N-isobutil-N-(5-metil-2-furilsofonil)amino]naftalen-2-iloximetil]cinámico, Ácido 4-[4,5-dimetil-2-[N(5-metil-2-furilsulfonil)-N-(2-propenil)amino]fenoximetil]benzoico, Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsofonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsofonil)-N-propilamino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-meilbenzoico, Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(5-metil-2-furilsofonil)amino]fenoximetil]benzoico, Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil]benzoico, Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(5-metil-2-furilsofonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino)-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolil)sulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico, N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide , 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2 -furyl) sulfonylamide, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl ) sulfonylamide, 4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 3-Methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [2- [N- (2-methyl-2-propenyl) -N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 3-Methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -2-naphthyloxymethyl] benzoic acid, 3-methyl-4- [6 - [- N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid, 4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzyl alcohol, 4- [6- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid, 4- [6- [N-methyl-N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N-ethyl-N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N- (5-methyl-2-furylsophonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid, 4- [4,5-Dimethyl-2- [N- (2-methyl-2-propenyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [6- [N- (5-methyl-2-furylsofonyl) N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N- (5-methyl-2-furylsophonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid, 3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [4,5-Dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] benzoic acid, 4- [4,5-dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] phenoxymethyl] benzoic acid, 4- [3- [N-Isopropyl-N- (5-methyl-2-furylsofonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid, 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsophonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid, 4- [3- [N-Isopropyl-N- (5-methyl-2-furylsophonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 3-Methyl-4- [3- [N-isopropyl-N- (5-methyl-2-furylsofonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 3-Methyl-4- [3- [N-isobutyl-N- (5-methyl-2-furylsophonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 4- [4,5-Dimethyl-2- [N (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] benzoic acid, 4- [4,5-Dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsophonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-dimethyl-2- [N- (5-methyl-2-furylsophonyl) -N-propylamino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid, 4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (5-methyl-2-furylsophonyl) amino] phenoxymethyl] benzoic acid, 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] benzoic acid, 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (5-methyl-2-furylsofonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino) -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolyl) sulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid,

N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4-cloro-5-metil-2-(4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4-cloro-5-metil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2tiazolil)sulfonilamida, Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2tiazolil)sulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2tiazolil)sulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[3-[N-isobuti]-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico, Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico, Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico, Ácido 4-[3-[N-isopropil-N-[2-(4-metiltiazolil)sulfonil]amino]naftalen-2-iloximetil]-3-metilbenzoico, Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico, Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico, Ácido 4-[4,5-dimetil-2-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-propil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-(2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico, Ácido 4-[6-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[3-[N-isobutil-N-[2-(4-metiltiazolil)sulfonil]amino]naftalen-2-iloximetil]3-metilbenzoico, Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico, Ácido 4-[6-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-propilamino]indan-5-iloximetil]benzoico, Ácido 4-[6-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide, N- [4-Chloro-5-methyl-2- (4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl ) sulfonylamide, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl -2 thiazolyl) sulfonylamide, 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) ) sulfonylamide, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2 -thiazolyl) sulfonylamide, N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide , N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide , N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) ) sulfonylamide, N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide, 4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 3-Methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-Methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 3-methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-Methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid 3-methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-Methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 3-Methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [3- [N-Isobuti] -N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid, 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid, 4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid, 4- [3- [N-Isopropyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid, 4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid, 4- [4,5-Dimethyl-2- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-dimethyl-2- [N-propyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methyl] -3-methylbenzoic acid, 4- [4,5-dimethyl-2- [N- (2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid, 4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [3- [N-Isobutyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] 3-methylbenzoic acid, 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid, 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid, 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid,

Ácido 3-metil-4-[6-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico, Ácido 3-metil-4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico, Ácido 3-metil-4-(6-[N-(4-metil-2-tiazolilsulfonil)-N-propilamino]indan-5-iloximetil]cinámico, Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, Ácido 3-cloro-4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico; Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 3-metoxi-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metoxi-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico, Ácido 4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, Ácido 4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, N-[4,5-dimetil-2-(2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-3-piridilsulfonilamida, N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida. 3-Methyl-4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid, 3-Methyl-4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid, 3-Methyl-4- (6- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid, 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isopropyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid; 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 3-Methoxy-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-Methoxy-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid, 4- [2- [N-Isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 4- [2- [N-Isopropyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, N- [4,5-dimethyl-2- (2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-3-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide, 3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide.

Ésteres: Esters:

Entre los compuestos de fórmula (I) de la presente invención, el compuesto de fórmula (I) se puede convertir al éster correspondiente por procedimientos de por sí conocidos. La conversión en alquil éster es útil, puesto que aumenta la estabilidad y absorbabilidad del compuesto. Se prefiere un éster alquílico C1-4. Puede prepararse el éster de fórmula (I-B) por procedimientos de por sí conocidos. También puede obtenerse en forma del compuesto de fórmula (I-A) en el procedimiento de preparación del compuesto en la presente invención. Among the compounds of formula (I) of the present invention, the compound of formula (I) can be converted to the corresponding ester by methods known per se. The conversion to alkyl ester is useful, since it increases the stability and absorbability of the compound. A C1-4 alkyl ester is preferred. The ester of formula (I-B) can be prepared by methods known per se. It can also be obtained in the form of the compound of formula (I-A) in the process of preparing the compound in the present invention.

Sales: You go out:

El compuesto de fórmula (I) de la presente invención se puede convertir en la sal correspondiente por un procedimiento ya conocido. Se prefiere una sal no-tóxica y soluble en agua. Una sal adecuada incluye, por ejemplo, una sal de metales alcalinos (potasio, sodio, etc.), una sal de metales alcalinotérreos (calcio, magnesio, etc.), una sal de amonio, una sal de aminas orgánicas farmacéuticamente aceptables (tetrametilamonio, trietilamina, metilamina, dimetilamina, ciclopentilamina, bencilamina, fenetilamina, piperidina, monoetanolamina, dietanolamina, tris(hidroximetil)metilamina, lisina, arginina, N-metil-D-glucamina, etc,). The compound of formula (I) of the present invention can be converted into the corresponding salt by a known procedure. A non-toxic and water soluble salt is preferred. A suitable salt includes, for example, an alkali metal salt (potassium, sodium, etc.), an alkaline earth metal salt (calcium, magnesium, etc.), an ammonium salt, a pharmaceutically acceptable organic amines salt (tetramethylammonium , triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) methylamine, lysine, arginine, N-methyl-D-glucamine, etc,).

Procedimiento para la preparación del compuesto de la presente invención: Process for the preparation of the compound of the present invention:

El compuesto de fórmula (I) de la presente invención puede prepararse por procedimientos descritos en el documento WO 98/27053 o de acuerdo con los esquemas de reacción indicados a continuación. A continuación, se describen detalles del procedimiento. The compound of formula (I) of the present invention can be prepared by procedures described in WO 98/27053 or according to the reaction schemes indicated below. Details of the procedure are described below.

En los esquemas, R es alquil C1-4, Tf es trifluorometanosulfonilo y los otros símbolos tienen los mismos significados que se han definido anteriormente en el presente documento. In the schemes, R is C1-4 alkyl, Tf is trifluoromethanesulfonyl and the other symbols have the same meanings as defined hereinbefore.

R: alquilo C1-4; R: C1-4 alkyl;

5 Ms : mesilo; Tf2O : ácido trifluorometanosulfónico anhídrido; Et: etilo; TCDI : 1,1'-tiocarbonildiimidazol. 5 Ms: mesyl; Tf2O: trifluoromethanesulfonic acid anhydride; Et: ethyl; TCDI: 1,1'-thiocarbonyldiimidazole.

10 Esquema de reacción (A) 10 Reaction scheme (A)

Esquema de reacción (B) Reaction Scheme (B)

5 Entre los compuestos de fórmula (I), cuando Ar es un anillo heterocíclico que tiene una parte básica, su haluro de sulfonilo correspondiente (el compuesto de fórmula (VIII)) descrito en el esquema de reacción (A) es susceptible de calentarse y se encontró que se descomponía fácilmente cuando se dejaba según estaba (véase Ejemplo de Comparación 1). Among the compounds of formula (I), when Ar is a heterocyclic ring having a basic part, its corresponding sulfonyl halide (the compound of formula (VIII)) described in the reaction scheme (A) is capable of being heated and It was found to decompose easily when left as it was (see Comparison Example 1).

10 En particular, es fácilmente previsible que un haluro de sulfonilo que tiene una parte básica, tal como un anillo heterocíclico que contiene un átomo de nitrógeno se descomponga fácilmente, puesto que los compuestos de haluro de sulfonilo son generalmente inestables frente a bases. In particular, it is easily predictable that a sulfonyl halide having a basic part, such as a heterocyclic ring containing a nitrogen atom, will readily decompose, since sulfonyl halide compounds are generally unstable against bases.

Por esto, al preparar un haluro de sulfonilo que tiene una parte básica, esto se ve afectado en que (1) es difícil aislar Therefore, when preparing a sulfonyl halide having a basic part, this is affected in that (1) it is difficult to isolate

15 a haluro de sulfonilo porque el haluro de sulfonilo afectado es inestable tras la evaporación del disolvente después de que termine la reacción y en que (2) es probable que el haluro de sulfonilo pueda descomponerse en el procedimiento de preparación de una sulfonamida a partir del mismo cuando se someta a una temperatura mayor que la temperatura ambiente durante un periodo de tiempo largo. 15 to sulfonyl halide because the affected sulfonyl halide is unstable after evaporation of the solvent after the end of the reaction and in which (2) it is likely that the sulfonyl halide can be decomposed in the process of preparing a sulfonamide from same when subjected to a temperature greater than room temperature for a long period of time.

Como se ha descrito anteriormente, cuando el haluro de sulfonilo se descompone fácilmente, es difícil determinar la cantidad real del haluro de sulfonilo y es engorroso tratarlo. Cuando el compuesto de sulfonamida se prepara sometiendo a una reacción de condensación con un compuesto de amina, se ve afectado el bajo rendimiento debido a la descomposición del haluro de sulfonilo en la producción en serie a escala industrial. As described above, when sulfonyl halide decomposes easily, it is difficult to determine the actual amount of sulfonyl halide and it is cumbersome to treat it. When the sulfonamide compound is prepared by undergoing a condensation reaction with an amine compound, the low yield is affected due to the decomposition of the sulfonyl halide in serial production on an industrial scale.

5 Como para el procedimiento para la preparación de una sulfonamida, la reacción de condensación con un haluro de sulfonilo y una amina se conoce generalmente. 5 As for the process for the preparation of a sulfonamide, the condensation reaction with a sulfonyl halide and an amine is generally known.

Se desvela un procedimiento para transformar un cloruro de sulfonilo en una sulfonamida o un éster de ácido A process for transforming a sulfonyl chloride into a sulfonamide or an acid ester is disclosed.

10 sulfónico mediante una adición de un imidazol a un cloruro de fenilsulfonilo seguido de N-metilación (J. Org. Chem., 57, 4775-4777 (1992)), y se describe que el procedimiento es útil en el caso de reacción con un nucleófilo que tiene baja nucleofilicidad o uno estéricamente impedido. Sin embargo, ni se describe ni se sugiere que los procedimientos mejoren la estabilidad del haluro de sulfonilo. 10 sulfonic by an addition of an imidazole to a phenylsulfonyl chloride followed by N-methylation (J. Org. Chem., 57, 4775-4777 (1992)), and it is described that the process is useful in the case of reaction with a nucleophile that has low nucleophilicity or a sterically hindered one. However, it is neither described nor suggested that the procedures improve the stability of the sulfonyl halide.

15 Los inventores de la presente invención han investigado para convertir un haluro de sulfonilo que tiene un anillo heterocíclico de la fórmula (III) en un compuesto más estable, descubriendo que el propósito se consiguió convirtiéndolo en los compuestos de las fórmulas (II-A) y (II-B) de acuerdo con el procedimiento para la preparación como se muestra en el siguiente esquema de reacción (C). The inventors of the present invention have investigated to convert a sulfonyl halide having a heterocyclic ring of the formula (III) into a more stable compound, discovering that the purpose was achieved by converting it into the compounds of the formulas (II-A) and (II-B) according to the procedure for the preparation as shown in the following reaction scheme (C).

20 Esquema de reacción C 20 Reaction scheme C

En el esquema de reacción (C), la etapa (a) es un procedimiento de conversión en un compuesto de sulfonilo estable In the reaction scheme (C), step (a) is a process of conversion into a stable sulfonyl compound

25 con 1-hidroxi-benzotriazol. Por ejemplo, se realiza con 1-hidroxibenzotriazol, en un disolvente orgánico (un éter (tbutil metil éter, éter dietílico, tetrahidrofurano, etc.), un disolvente halógeno (cloruro de metileno, cloroformo, etc.), etc.) en presencia de una base (trietilamina, diisopropiletilamina, dimetilaminopiridina, piridina, etc.), a una temperatura de -20 a 30 ºC. 25 with 1-hydroxy-benzotriazole. For example, it is carried out with 1-hydroxybenzotriazole, in an organic solvent (an ether (tutyl methyl ether, diethyl ether, tetrahydrofuran, etc.), a halogen solvent (methylene chloride, chloroform, etc.), etc.) in the presence of a base (triethylamine, diisopropylethylamine, dimethylaminopyridine, pyridine, etc.), at a temperature of -20 to 30 ° C.

30 La etapa (b) también es un procedimiento para preparar un compuesto de sulfonilo estable; por ejemplo, se realiza en un disolvente orgánico (un éter (t-butil metil éter, éter dietílico, tetrahidrofurano, etc.), un disolvente halógeno (cloruro de metileno, cloroformo, etc.), etc.) con N-metilimidazol a una temperatura de -20 a 30 ºC. Step (b) is also a process for preparing a stable sulfonyl compound; for example, it is carried out in an organic solvent (an ether (t-butyl methyl ether, diethyl ether, tetrahydrofuran, etc.), a halogen solvent (methylene chloride, chloroform, etc.), etc.) with N-methylimidazole a a temperature of -20 to 30 ° C.

Estas etapas (a) y (b) se realizan preferentemente en una condición anhidra en una atmósfera de gas inerte. These steps (a) and (b) are preferably performed in an anhydrous condition in an inert gas atmosphere.

35 En particular, cuando el compuesto de fórmula (III) es inestable al calentamiento, cada una de las etapas (a) y (b) puede realizarse sin concentrar la solución preparada de haluro de sulfonilo. In particular, when the compound of formula (III) is unstable upon heating, each of steps (a) and (b) can be carried out without concentrating the prepared sulfonyl halide solution.

El haluro de sulfonilo de la fórmula (III) se obtiene en forma de una solución después de la preparación y puede The sulfonyl halide of the formula (III) is obtained in the form of a solution after preparation and can

40 aislarse generalmente concentrando la solución. Si se exponen los materiales a alta temperatura mientras se concentran, existe una posibilidad de que haluro de sulfonilo pueda descomponerse por calentamiento a gran escala, aunque no hay ningún problema en particular a pequeña escala (véase Ejemplo Comparativo). Por tanto, la trasformación en el compuesto de las fórmulas (II-A) o (II-B) son concentrar la solución, asegura una baja degradabilidad de un cloruro de sulfonilo con su reactividad alta (véanse Ejemplos 7 y 8). 40 generally isolate by concentrating the solution. If the materials are exposed to high temperature while concentrating, there is a possibility that sulfonyl halide can be decomposed by large-scale heating, although there is no particular problem on a small scale (see Comparative Example). Therefore, the transformation in the compound of the formulas (II-A) or (II-B) is to concentrate the solution, ensures a low degradability of a sulfonyl chloride with its high reactivity (see Examples 7 and 8).

45 En el esquema de reacción, el haluro de sulfonilo de fórmula (III) usado como material de partida se conoce en sí mismo o puede prepararse fácilmente por un procedimiento convencional a partir de un compuesto conocido. Los otros materiales de partida y reactivos en la presente invención se conocen por sí mismos o pueden prepararse de acuerdo con procedimientos convencionales. In the reaction scheme, the sulfonyl halide of formula (III) used as a starting material is known per se or can easily be prepared by a conventional process from a known compound. The other starting materials and reagents in the present invention are known per se or can be prepared according to conventional procedures.

50 El esquema de reacción (C) puede proporcionar un procedimiento para la preparación del compuesto de fórmula (VIII), en el que Ar es un anillo heterocíclico básico. El procedimiento de la presente invención es útil para la estabilización de un compuesto, no sólo de un intermedio del compuesto de fórmula (I) inestable, si no también de un cloruro de sulfonilo inestable con un anillo heterocíclico básico. The reaction scheme (C) can provide a process for the preparation of the compound of formula (VIII), wherein Ar is a basic heterocyclic ring. The process of the present invention is useful for the stabilization of a compound, not only of an intermediate of the compound of formula (I) unstable, but also of an unstable sulfonyl chloride with a basic heterocyclic ring.

En la presente invención, Ar es piridilo, 5-metil-2-furilo o tiazolilo, opcionalmente sustituido con metilo. In the present invention, Ar is pyridyl, 5-methyl-2-furyl or thiazolyl, optionally substituted with methyl.

En el presente documento alquilo C1-8, como un sustituyente de Ar', es metilo, etilo, propilo, butilo, pentilo, hexilo, heptilo, octilo o isómeros de los mismos. Herein C1-8 alkyl, as a substituent of Ar ', is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl or isomers thereof.

En el presente documento, alcoxi C1-8 es metoxi, etoxi, propoxi, butoxi, pentiloxi, hexiloxi, heptiloxi, octiloxi o isómeros de los mismos. Here, C1-8 alkoxy is methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy or isomers thereof.

En el presente documento, átomo de halógeno, como un sustituyente de Ar', es un átomo de flúor, cloro, bromo o yodo. Here, halogen atom, as an Ar 'substituent, is a fluorine, chlorine, bromine or iodine atom.

En el presente documento, anillo carbocíclico C3-10, como un sustituyente de Ar', es anillo ciclopropano, ciclobutano, ciclopentano, ciclohexano, cicloheptano, ciclopenteno, ciclohexeno, ciclopentadieno, ciclohexadieno, benceno, pentaleno, indeno, naftaleno, bifenileno, perhidropentaleno, perhidroindeno, perhidronaftaleno, etc. Hereby, C3-10 carbocyclic ring, as a substituent of Ar ', is cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene, pentalene, indene, naphthalene, biphenylene, perhydropene ring. perhydroindene, perhydronaphthalene, etc.

En el presente documento, anillo heterocíclico de 5 a 10 miembros, como un sustituyente de Ar', es un anillo mono o bicíclico de 5 a 10 miembros que contiene de 1 a 4 átomos de nitrógeno), de 1 a 2 átomos de azufre y/o 1 átomo de azufre, incluyendo arilo mono o bicíclico de 5 a 10 miembros o un anillo parcial o totalmente saturad del mismo. Here, a 5 to 10 membered heterocyclic ring, as an Ar 'substituent, is a 5 to 10 membered mono or bicyclic ring containing 1 to 4 nitrogen atoms), 1 to 2 sulfur atoms and / or 1 sulfur atom, including mono or bicyclic aryl of 5 to 10 members or a partially or fully saturated ring thereof.

En el presente documento, arilo mono o biheterocíclico de 5 a 10 miembros que contiene de 1 a 4 átomos de nitrógeno, de 1 a 2 átomos de oxígeno y/o 1 átomo de azufre como un sustituyente de Ar', es un anillo pirrol, imidazol, triazol, tetrazol, pirazol, piridina, pirazina, pirimidina, piridazina, azepina, diazepina, furano, pirano, oxepina, oxazepina, tiofeno, tiaina (tiopirano), tiepina, oxazol, isoxazol, tiazol, isotiazol, oxadiazol, oxazina, oxadiazina, oxazepina, oxadiazepina, tiadiazol, tiazina, tiadiazina, tiazepina, tiadiazepina, indol, isoindol, benzofurano, isobenzofurano, benzotiofeno, isobenzotiofeno, indazol, quinolina, isoquinolina, ftalazina, naftiridina, quinoxalina, quinazolina, cinnolina, benzoxazol, benzotiazol, benzoimidazol, etc. Here, 5 or 10-membered mono or biheterocyclic aryl containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom as an Ar 'substituent, is a pyrrole ring, imidazole, triazole, tetrazol, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepine, oxazepine, thiophene, thiaine (thiopyran), tiepine, oxazole, isoxazole, thiazole, isothiazol, oxadiazol, oxadiazol , oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine, tiadiazepina, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, benzoxazole, benzothiazole, benzimidazole, etc. .

En el presente documento, una anillo mono o biheterocíclico de 5 a 10 miembros parcial o totalmente saturado del mismo, es un anillo de pirrolina, pirrolidina, imidazolina, imidazolidina, triazolina, triazolidina, tetrazolina, tetrazolidina, pirazolina, pirazolidina, piperidina, piperazina, tetrahidropiridina, tetrahidropirimidina, tetrahidropiridazina, dihidrofurano, tetrahidrofurano, dihidropirano, tetrahidropirano, dihidrotiofeno, tetrahidrotiofeno, dihidrotiaina (dihidrotiopirano), tetrahidrotiaina (tetrahidrotiopirano), oxazolina (dihidrooxazol), oxazolidina (tetrahidrooxazol), dihidroisoxazol, tetrahidroisoxazol, oxadiazolina (dihidrooxadiazol), oxadiazolidina (tetrahidrooxadiazol), tiazolina (dihidrotiazol), tiazolidina (tetrahidrotiazol), dihidroisotiazol, tetrahidroisotiazol, morfolina, tiomorfolina, indolina, isoindolina, dihidrobenzofurano, perhidrobenzofurano, dihidroisobenzofurano, perhidroisobenzofurano, dihidrobenzotiofeno, perhidrobenzotiofeno, dihidroisobenzotiofeno, perhidroisobenzotiofeno, dihidroindazol, perhidroindazol, dihidroquinolina, tetrahidroquinolina, perhidroquinolina, dihidroisoquinolina, tetrahidroisoquinolina, perhidroisoquinolina, dihidroftalazina, tetrahidroftalazina, perhidroftalazina, dihidronaftiridina, tetrahidronaftiridina, perhidronaftiridina, dihidroquinoxalina, tetrahidroquinoxalina, perhidroquinoxalina, dihidroquinazolina, tetrahidroquinazolina, perhidroquinazolina, dihidrocinnolina, tetrahidrocinnolina, perhidrocinnolina, dihidrobenzoxazol, perhidrobenzoxazol, dihidrobenzotiazol, perhidrobenzotiazol, dihidrobenzoimidazol, perhidrobenzoimidazol, benzofurazano, benzotiadiazol, benzotriazol, imidazotiazol, dioxolano, dioxano, dioxadina, etc. Here, a mono or bi-heterocyclic ring of 5 to 10 members partially or fully saturated therein, is a pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine ring, tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihidrotiaina (dihydrothiopyran), tetrahidrotiaina (tetrahydrothiopyran), oxazoline (dihydrooxazole), oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole, oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahidrooxadiazol ), thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole), dihydroisothiazol, tetrahydroisothiazole, morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran, perhidrobenzofurano, dihydroisobenzofuran, perhidroisobenzofurano, dihydrobenzothiophene, perhidrobenzotiofeno, dihidroisobenzotiofeno, perhidroisobenzotiofeno, dihydroindazole, perhidroindazol, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline, dihydrophthalazine tetrahidroftalazina, perhidroftalazina, dihydronaphthyridine, tetrahydronaphthyridine, perhidronaftiridina, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhidroquinazolina, dihidrocinnolina, tetrahidrocinnolina, perhidrocinnolina, dihydrobenzoxazol, perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzoimidazole, perhydrobenzoimidazole, benzofurazano, benzothiadiazole, benzotriazole, imidazothiazole, dioxolane, dioxane, dioxadine, etc.

En el presente documento, Ar' es preferiblemente un anillo heterocíclico básico de 5 a 10 miembros que contiene de 1 a 4 átomos de nitrógeno y se prefieren más anillos tiazol, isotiazol, isoxazol, pirazina, pirimidina, piridazina, piridina, pirrol, imidazol, pirazol, triazol, indol, indolina, purina, quinolina, isoquinolina, ftalazina, naftiridina, quinoxalina, cinnolina, pirrolidina, pirrolina, imidazolidina, imidazolina y pirazolina. Los más preferidos son anillo piridina o tiazol. Here, Ar 'is preferably a 5 to 10-membered basic heterocyclic ring containing 1 to 4 nitrogen atoms and thiazole, isothiazole, isoxazole, pyrazine, pyrimidine, pyridazine, pyridine, pyrrole, imidazole rings are more preferred. pyrazole, triazole, indole, indoline, purine, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, cinnoline, pyrrolidine, pyrroline, imidazolidine, imidazoline and pyrazoline. Most preferred are pyridine or thiazole ring.

Los materiales de partida y reactivos en la presente invención se conocen per se o pueden prepararse por procedimientos conocidos. Los compuestos de las fórmulas (III), (IV), (V), (VIII) y (X) se conocen per se o pueden prepararse por procedimientos conocidos. The starting materials and reagents in the present invention are known per se or can be prepared by known procedures. The compounds of the formulas (III), (IV), (V), (VIII) and (X) are known per se or can be prepared by known procedures.

En cada reacción en la presente memoria descriptiva, pueden purificarse productos obtenidos por técnicas conocidas. Por ejemplo, puede realizarse purificación por destilación a presión atmosférica o reducida, por cromatografía líquida de alto rendimiento, por cromatografía de capa fina o por cromatografía en columna usando gel de sílice o silicato de magnesio, por lavado o por recristalización. La purificación puede realizarse después de cada reacción o después de una serie de reacciones. In each reaction herein, products obtained by known techniques can be purified. For example, purification can be carried out by distillation at atmospheric or reduced pressure, by high performance liquid chromatography, by thin layer chromatography or by column chromatography using silica gel or magnesium silicate, by washing or by recrystallization. Purification can be performed after each reaction or after a series of reactions.

Actividad farmacológica de los compuestos de la presente invención: Pharmacological activity of the compounds of the present invention:

El compuesto de fórmula (I) de la presente invención puede unirse fuertemente al receptor EP1, que es un subtipo de receptor de prostaglandina E2 y muestra actividad antagonista. Como se ha mencionado anteriormente en el presente documento, se sabe que el receptor EP1 está relacionado con la inducción de dolor, pirexia (inducción de fiebre), diuresis o actividad contráctil de la vejiga. Por lo tanto, el compuesto de fórmula (I), un éster alquílico del mismo y una sal no tóxica del mismo, que puede antagonizar este receptor, es útil como analgésico, como agente antipirético o como agente para la prevención y/o tratamiento de la polaquiuria (vejiga neurogénica, vejiga nerviosa, vejiga estimulada (vejiga irritable), inestabilidad del detrusor, disuria que acompaña a prostatomegalia), acraturesis (incontinencia urinaria), síndrome de enfermedad del tracto urinario inferior. Además, el compuesto de la presente invención apenas se une a los otros subtipos de PGE2 y es de esperar que proporcione un agente sin efectos secundarios. The compound of formula (I) of the present invention can be strongly bound to the EP1 receptor, which is a subtype of prostaglandin E2 receptor and shows antagonistic activity. As mentioned earlier herein, it is known that the EP1 receptor is related to pain induction, pyrexia (fever induction), diuresis or contractile bladder activity. Therefore, the compound of formula (I), an alkyl ester thereof and a non-toxic salt thereof, which can antagonize this receptor, is useful as an analgesic, as an antipyretic agent or as an agent for the prevention and / or treatment of Polachiuria (neurogenic bladder, nervous bladder, stimulated bladder (irritable bladder), detrusor instability, dysuria that accompanies prostatomegaly), acraturesis (urinary incontinence), lower urinary tract disease syndrome. In addition, the compound of the present invention barely binds to the other subtypes of PGE2 and is expected to provide an agent without side effects.

5 Se sabe que un antagonista de EP1 posee un efecto supresor sobre los focos de cripta aberrantes y la formación de pólipos intestinales, por lo que indica una actividad antitumoral eficaz. 5 It is known that an EP1 antagonist has a suppressive effect on aberrant crypt foci and the formation of intestinal polyps, thus indicating an effective antitumor activity.

El experimento descrito a continuación muestra evidentemente que el compuesto de la presente invención está 10 menos afectado por la unión a proteínas, por lo que tiene una actividad in vivo satisfactoria. The experiment described below evidently shows that the compound of the present invention is less affected by protein binding, so it has satisfactory in vivo activity.

Ensayo experimental farmacológico Pharmacological experimental trial

(i) Ensayo de unión usando células de expresión de subtipos de receptores de prostanoides (i) Binding assay using prostanoid receptor subtype expression cells

15 La preparación de la fracción de membrana se realizó de acuerdo con el método de Sugimoto et al. (J. Biol. Chem, 267, 6466-6463 (1992)), usando expresión en células CHO de subtipos de receptores de prostanoides (EP1, EP2, EP3a o EP4 de ratón). 15 The preparation of the membrane fraction was performed according to the method of Sugimoto et al. (J. Biol. Chem, 267, 6466-6463 (1992)), using expression in CHO cells of subtypes of prostanoid receptors (EP1, EP2, EP3a or mouse EP4).

20 La mezcla de ensayo convencional que contenía la fracción de membrana (0,5 mg/ml) y 3H-PGE2 en un volumen final de 200 μl se incubó durante 1 hora a temperatura ambiente. La reacción se terminó por la adición de tampón enfriado en hielo (3 ml). La mezcla se filtró rápidamente a través de un filtro de vidrio (GF/B). La radiactividad asociada con el filtro se midió por recuento de centelleo de líquidos. The conventional test mixture containing the membrane fraction (0.5 mg / ml) and 3H-PGE2 in a final volume of 200 μl was incubated for 1 hour at room temperature. The reaction was terminated by the addition of ice-cold buffer (3 ml). The mixture was quickly filtered through a glass filter (GF / B). The radioactivity associated with the filter was measured by liquid scintillation counting.

25 Los valores de Kd y Bmáx se determinaron a partir de gráficos de Scatchard (Ann. N.Y, Acad. Sci., 51, 660 (1949)). La unión no específica se calculó como la unión en presencia de un exceso (2,5 μM) de PGE2 no marcada. En el experimento para la competición de la unión de 3H-PGE2 específica por el compuesto de la presente invención, se añadieron 3H-PGE2 (2,5 nM) y el compuesto de la presente invención. En todas las reacciones se usó el siguiente tampón 25 The values of Kd and Bmax were determined from Scatchard graphs (Ann. N.Y, Acad. Sci., 51, 660 (1949)). Non-specific binding was calculated as binding in the presence of an excess (2.5 μM) of unlabeled PGE2. In the experiment for the competition of specific 3H-PGE2 binding by the compound of the present invention, 3H-PGE2 (2.5 nM) and the compound of the present invention were added. In all reactions the following buffer was used

30 Tampón: fosfato potásico (pH 6,0, 10 mM), EDTA (1 mM), MgCl2 (10 mM) y NaCl (0,1 M). 30 Buffer: potassium phosphate (pH 6.0, 10 mM), EDTA (1 mM), MgCl2 (10 mM) and NaCl (0.1 M).

La constante de disociación Ki (μM) de cada compuesto, se calculó por la siguiente ecuación*. The dissociation constant Ki (μM) of each compound was calculated by the following equation *.

35 Ki=CI50/(1+([C)]/Kd)) 35 Ki = IC50 / (1 + ([C)] / Kd))

en la que [C] es la concentración de 3H-PGE2 usada en la reacción in which [C] is the concentration of 3H-PGE2 used in the reaction

Los resultados se muestran en la Tabla 1. 40 Tabla 1 The results are shown in Table 1. 40 Table 1

Compuestos Compounds: Ki (μM) Ki (μM)

Compuestos de la presente invención Ejemplo 2 Compounds of the present invention Example 2: 0,0042 0.0042

Ejemplo 2 (6) Example 2 (6): 0,00032 0.00032

Ejemplo 2 (32) Example 2 (32): 0,0079 0.0079

Ejemplo 2 (33) Example 2 (33): 0,0066 0.0066

Ejemplo 2 (87) Example 2 (87): 0,0014 0.0014

Ejemplo 2 (94) Example 2 (94): 0,0039 0.0039

Ejemplo 3 (11) Example 3 (11): 0,0023 0.0023

Ejemplo 3 (30) Example 3 (30): 0,0008 0.0008

Ejemplo 4 (14) Example 4 (14): 0,0008 0.0008

Compuestos de la técnica relacionada (documento WO98/27053) Ejemplo 18 (93) Compounds of the related art (WO98 / 27053) Example 18 (93): 0,0008 0.0008

Ejemplo 18 (113) Example 18 (113): 0,0055 0.0055

Ejemplo 18 (125) Example 18 (125): 0,0013 0.0013

Ejemplo 18 (121) Example 18 (121): 0,0010 0.0010

Comentarios: Comments:

Se confirma que la afinidad de unión del compuesto de fórmula (I) de la presente invención a un receptor de subtipo 45 EP1 es un equivalente a la del compuesto descrito específicamente en el documento WO98/27053 mencionado anteriormente. It is confirmed that the binding affinity of the compound of formula (I) of the present invention to a subtype receptor EP1 is equivalent to that of the compound specifically described in WO98 / 27053 mentioned above.

(ii) Medición experimental de la actividad de antagonismo del receptor usando células que expresan el subtipo de receptor de prostanoides EP1 en presencia de BSA (albúmina de suero bovino). (ii) Experimental measurement of receptor antagonism activity using cells expressing the subtype of prostanoid receptor EP1 in the presence of BSA (bovine serum albumin).

Las células que expresaban el receptor EP1 de ratón se sembraron a 1 × 104 células/pocillo en placas de 96 pocillos Cells expressing the mouse EP1 receptor were seeded at 1 × 104 cells / well in 96-well plates

5 y se cultivaron durante 2 días con FBS (suero bovino fetal) al 10%/modificación alfa de medio esencial mínimo Eagle (αMEM) en la incubadora (37 ºC, 5% de CO2). Las células de cada pocillo se aclararon con tampón fosfato (PBS(-)), y se añadió tampón de carga. Después de la incubación durante 1 hora, se desechó el tampón de carga. Después de la adición del tampón de ensayo a cada pocillo, las células se incubaron en un sitio oscuro a temperatura ambiente durante 1 hora. Después de la adición de un compuesto de la presente invención (10 μl) y PGE2 (10 μl) 5 and were cultured for 2 days with 10% FBS (fetal bovine serum) / alpha modification of Eagle minimum essential medium (αMEM) in the incubator (37 ° C, 5% CO2). The cells in each well were rinsed with phosphate buffer (PBS (-)), and loading buffer was added. After incubation for 1 hour, the loading buffer was discarded. After the addition of the assay buffer to each well, the cells were incubated in a dark place at room temperature for 1 hour. After the addition of a compound of the present invention (10 μl) and PGE2 (10 μl)

10 que se prepararon con tampón de ensayo, se midió la concentración de calcio intracelular con un sistema de exploración de fármacos con fluorescencia (FDSS-4000, Hamamatsu Photonics). Se midió un par de intensidades de fluorescencia emitidas a 500 nm por una longitud de onda de excitación de 340 nm y 380 nm. 10 which were prepared with assay buffer, the intracellular calcium concentration was measured with a fluorescent drug scanning system (FDSS-4000, Hamamatsu Photonics). A pair of fluorescence intensities emitted at 500 nm was measured by an excitation wavelength of 340 nm and 380 nm.

La actividad antagonista de EP1 se estimó como el porcentaje de inhibición del aumento de la concentración de 15 calcio intracelular inducida por PGE2 (100 nM). The antagonistic activity of EP1 was estimated as the percentage of inhibition of the increase in the concentration of intracellular calcium induced by PGE2 (100 nM).

Tampón de carga: FBS al 10%/αMEM que contiene 5 μM de Fura 2/AM, 20 μM de indometacina, 2,5 mM de probenecid Tampón de ensayo: solución salina equilibrada de Hank (HBSS) que contiene BSA al 1% (p/v), 2 μM de Loading buffer: 10% FBS / αMEM containing 5 μM Fura 2 / AM, 20 μM indomethacin, 2.5 mM probenecid Test buffer: Hank's balanced saline solution (HBSS) containing 1% BSA ( p / v), 2 μM of

20 indometacina, 2,5 mM de probenecid y 10 mM de HEPES-NaOH 20 indomethacin, 2.5 mM probenecid and 10 mM HEPES-NaOH

Los resultados se muestran en la tabla 2. Results are shown in table 2.

Tabla 2 Table 2

Compuestos Compounds: CI50 (μM) IC50 (μM)

Compuestos de la presente invención Ejemplo 2 Compounds of the present invention Example 2: 0,0078 0.0078

Ejemplo 2 (6) Example 2 (6): 0,0072 0.0072

Ejemplo 2 (32) Example 2 (32): 0,021 0.021

Ejemplo 2 (33) Example 2 (33): 0,0041 0.0041

Ejemplo 2 (87) Example 2 (87): 0,0073 0.0073

Ejemplo 2 (94) Example 2 (94): 0,0092 0.0092

Ejemplo 3 (11) Example 3 (11): 0,0049 0.0049

Ejemplo 3 (30) Example 3 (30): 0,0037 0.0037

Ejemplo 4 (14) Example 4 (14): 0,0071 0.0071

Compuestos de la técnica relacionada (documento WO98/27053) Ejemplo 18 (93) Compounds of the related art (WO98 / 27053) Example 18 (93): 0,20 0.20

Ejemplo 18 (113) Example 18 (113): 0,47 0.47

Ejemplo 18 (125) Example 18 (125): 1,34 1.34

Ejemplo 18 (121) Example 18 (121): 0,26 0.26

25 Comentarios: 25 Comments:

En el experimento coexistente con proteínas (medición de actividad de señalización en células), el compuesto de fórmula (I) de la presente invención indicó una actividad de inhibición de la señalización diez veces mayor que el In the coexisting experiment with proteins (measurement of signaling activity in cells), the compound of formula (I) of the present invention indicated a signaling inhibition activity ten times greater than the

30 compuesto descrito específicamente en el documento WO98/27053, o mayor. Compound specifically described in WO98 / 27053, or greater.

Se muestra que el compuesto descrito específicamente en el documento WO98/27053 se ve afectado por la unión a proteínas al reducirse su actividad en coexistencia con proteínas del suero. Por otra parte, también se muestra que todos los compuestos de fórmula (I) de la presente invención se ven menos afectados por proteínas coexistentes, y It is shown that the compound specifically described in WO98 / 27053 is affected by protein binding by reducing its activity in coexistence with whey proteins. On the other hand, it is also shown that all the compounds of formula (I) of the present invention are less affected by coexisting proteins, and

35 su actividad se reduce menos. 35 its activity is reduced less.

(iii) Experimento para evaluar la inhibición del aumento inducido por sulprostona de la presión intravesical de vejigas en ratas. (iii) Experiment to assess the inhibition of sulprostone-induced increase in intravesical bladder pressure in rats.

40 Se anestesiaron ratas hembra (Wistar) con uretano y sus dos uréteres se ligaron y se cortaron en el lado renal. Se hizo una incisión en la parte superior de la vejiga urinaria y se insertó un catéter. El otro extremo del catéter se conectó al transductor de presión y la bomba de infusión. Se registró el reflejo miccional repetido, que se indujo por infusión continua de tampón citrato (pH 3,5) en la vejiga. El aumento de la presión de micción se indujo por la inyección subcutánea de diclofenaco (5 mg/kg) y sulprostona (300 μg/kg). Como dicho efecto de aumento no se 40 Female rats (Wistar) were anesthetized with urethane and their two ureters were ligated and cut on the renal side. An incision was made in the upper part of the urinary bladder and a catheter was inserted. The other end of the catheter was connected to the pressure transducer and the infusion pump. The repeated voiding reflex was recorded, which was induced by continuous infusion of citrate buffer (pH 3.5) into the bladder. The increase in urination pressure was induced by subcutaneous injection of diclofenac (5 mg / kg) and sulprostone (300 μg / kg). As this increase effect is not

45 observó con el tratamiento de agonista de EP3, se consideró que este aumento se debía a la activación del receptor EP1. Los efectos inhibidores del compuesto de la presente invención sobre este aumento de presión intravesical se midieron durante 60 minutos después de la administración intraduodenal (2 ml/kg). 45 observed with the treatment of EP3 agonist, it was considered that this increase was due to the activation of the EP1 receptor. The inhibitory effects of the compound of the present invention on this increase in intravesical pressure were measured for 60 minutes after intraduodenal administration (2 ml / kg).

La Tabla 3 muestra el porcentaje de inhibición de aumento de presión intravesical 40 minutos después de la administración (1 mg/kg). Table 3 shows the percentage of intravesical pressure increase inhibition 40 minutes after administration (1 mg / kg).

Tabla 3 Table 3

Compuestos Compounds: inhibición (%) (40 minutos después) inhibition (%) (40 minutes later)

Ejemplo 2 Example 2: 68 ± 1 68 ± 1

Ejemplo 2 (33) Example 2 (33): 79 ± 11 79 ± 11

5 Comentarios: 5 Comments:

Se confirma que el compuesto de fórmula (I) de la presente invención indicó un efecto supresor más fuerte que el del compuesto descrito específicamente en el documento WO98/27053 en el experimento in vivo, y que mostró una 10 actividad eficaz. It is confirmed that the compound of formula (I) of the present invention indicated a stronger suppressive effect than that of the compound specifically described in WO98 / 27053 in the experiment in vivo, and that it showed an effective activity.

(iv) Experimento para evaluar la actividad antagonista sobre el aumento del volumen de orina y del número de micciones inducido por sulprostona a ratas. (iv) Experiment to evaluate the antagonistic activity on the increase in urine volume and the number of urination induced by sulprostone in rats.

15 Se usaron ratas macho (CD (SD) IGS) y se midieron el número de micciones y el volumen de orina por medio de un sistema de medición del volumen de micción (Neuroscience). 15 Male rats (CD (SD) IGS) were used and the number of urination and urine volume was measured by means of a urination volume measurement system (Neuroscience).

Se administró por vía oral un compuesto de la presente invención (4 ml/kg) y, 30 minutos después, se administró por vía subcutánea sulprostona (200 μg/4 ml/kg). El número de micciones y el volumen de orina se supervisaron de 20 forma continua durante 3 horas desde la administración de sulprostona. A compound of the present invention (4 ml / kg) was orally administered and, 30 minutes later, sulprostone (200 μg / 4 ml / kg) was administered subcutaneously. Urination number and urine volume were monitored continuously for 3 hours from sulprostone administration.

El porcentaje de inhibición de cada compuesto se calculó por la siguiente ecuación. The percent inhibition of each compound was calculated by the following equation.

25 Comentarios: 25 Comments:

Se confirma que el compuesto de fórmula (I) de la presente invención indicó un efecto de supresión más fuerte que el del compuesto descrito específicamente en el documento WO98/27053 en el experimento in vivo. It is confirmed that the compound of formula (I) of the present invention indicated a stronger suppression effect than that of the compound specifically described in WO98 / 27053 in the in vivo experiment.

30 Toxicidad: 30 Toxicity:

La toxicidad del compuesto de la presente invención es muy baja y, por lo tanto, se confirma que el compuesto es seguro para uso médico. The toxicity of the compound of the present invention is very low and, therefore, it is confirmed that the compound is safe for medical use.

35 Industrial Applicability

Aplicación a productos farmacéuticos: Application to pharmaceutical products:

40 Por lo tanto, el compuesto de fórmula (I) de la presente invención, un éster alquílico del mismo y una sal no tóxica del mismo, que antagonizan el receptor EP1, se consideran útiles como analgésicos, como agentes antipiréticos o como agentes para el tratamiento de la polaquiuria (vejiga neurogénica, vejiga nerviosa, vejiga estimulada (vejiga irritable), inestabilidad del detrusor, disuria que acompaña a prostatomegalia), acraturesis (incontinencia urinaria), y síndrome de enfermedad del tracto urinario inferior. Además, el compuesto de la presente invención apenas se une Therefore, the compound of formula (I) of the present invention, an alkyl ester thereof and a non-toxic salt thereof, which antagonize the EP1 receptor, are considered useful as analgesics, as antipyretic agents or as agents for the Treatment of polaquiuria (neurogenic bladder, nerve bladder, stimulated bladder (irritable bladder), detrusor instability, dysuria that accompanies prostatomegaly), acraturesis (urinary incontinence), and lower urinary tract disease syndrome. In addition, the compound of the present invention barely binds

45 a los otros subtipos de PGE2 y es de esperar que proporcione un agente con pocos efectos secundarios. 45 to the other subtypes of PGE2 and is expected to provide an agent with few side effects.

También se sabe que un antagonista de EP1 posee un efecto supresor sobre focos de cripta aberrantes y la formación de pólipos intestinales, por consiguiente indica una actividad antitumoral eficaz. It is also known that an EP1 antagonist has a suppressive effect on aberrant crypt foci and the formation of intestinal polyps, thus indicating an effective antitumor activity.

50 El compuesto de fórmula (I) de la presente invención, y una sal no tóxica del mismo, puede administrarse en combinación con otros medicamentos con el objetivo de The compound of formula (I) of the present invention, and a non-toxic salt thereof, can be administered in combination with other medicaments for the purpose of

1) complementar y/o aumentar el efecto de prevención y/o tratamiento del compuesto, 2) mejorar la farmacocinética y/o la absorción del compuesto, reducir la dosis y/o 3) aliviar un efecto secundario del compuesto 1) complement and / or increase the effect of prevention and / or treatment of the compound, 2) improve the pharmacokinetics and / or absorption of the compound, reduce the dose and / or 3) relieve a side effect of the compound

El compuesto de fórmula (I) puede administrarse en combinación con otros medicamentos como una composición en un producto farmacéutico que comprende estos componentes, o pueden administrarse por separado. En el caso de la administración por separado, pueden administrarse simultáneamente o con un lapso de tiempo. En la administración con un lapso de tiempo, el compuesto de fórmula (I) puede administrarse antes, seguido de la administración de los otros medicamentos. Como alternativa, los otros medicamentos pueden administrarse antes, seguidos de la administración del compuesto de fórmula (I). Las vías de administración pueden ser iguales o diferentes. The compound of formula (I) may be administered in combination with other medicaments as a composition in a pharmaceutical product comprising these components, or they may be administered separately. In the case of separate administration, they can be administered simultaneously or with a period of time. In administration with a period of time, the compound of formula (I) may be administered before, followed by the administration of the other medicaments. Alternatively, the other medications can be administered before, followed by the administration of the compound of formula (I). The routes of administration may be the same or different.

El fármaco de combinación anterior tiene el efecto de complementar y/o aumentar el efecto de prevención y/o tratamiento de enfermedades del compuesto de fórmula (I). The above combination drug has the effect of complementing and / or increasing the disease prevention and / or treatment effect of the compound of formula (I).

Por ejemplo, los otros medicamentos que complementan y/o aumentan el efecto del compuesto de fórmula (I) para la prevención y/o tratamiento de polaquiuria (micción frecuente) son fármacos anticolinérgicos, agentes antidepresivos tricíclicos, agonistas de α, antagonistas de α1, agonistas de GABA, antidiuréticos, hormonas anti-androgénicas, hormonas del cuerpo lúteo, antagonistas de NK1, agonistas de β3, antagonistas de P2X, agentes de apertura de los canales de potasio, LPA, antagonistas de EP3, capsaicina, resiniferatoxina, inhibidores de 5α-reductasa, etc. For example, the other drugs that complement and / or increase the effect of the compound of formula (I) for the prevention and / or treatment of polaquiuria (frequent urination) are anticholinergic drugs, tricyclic antidepressant agents, α agonists, α1 antagonists, GABA agonists, antidiuretics, anti-androgenic hormones, corpus luteum hormones, NK1 antagonists, β3 agonists, P2X antagonists, potassium channel opening agents, LPA, EP3 antagonists, capsaicin, resiniferatoxin, 5α inhibitors -reductase, etc.

Por ejemplo, otros medicamentos que son útiles para complementar y/o aumentar el efecto del compuesto de fórmula (I) para la prevención y/o tratamiento de algia son opiáceos, gabapentina, pregabalina, antagonistas de α2, antagonistas de NMDA, bloqueantes de los canales de sodio resistentes a TTX, antagonistas de VR1, antagonistas de nociceptina, antagonistas de P2X, antagonistas de IP, antagonistas de EP3, bloqueantes de los canales de calcio de tipo N, inhibidores de iNOS, etc. For example, other medications that are useful to supplement and / or increase the effect of the compound of formula (I) for the prevention and / or treatment of algia are opiates, gabapentin, pregabalin, α2 antagonists, NMDA antagonists, blockers of TTX-resistant sodium channels, VR1 antagonists, nociceptin antagonists, P2X antagonists, IP antagonists, EP3 antagonists, N-type calcium channel blockers, iNOS inhibitors, etc.

No está limitada en particular la relación de pesos del compuesto de fórmula (I) y los otros medicamentos. In particular, the weight ratio of the compound of formula (I) and the other medicaments is not limited.

Los otros medicamentos pueden administrarse en combinación de dos o más arbitrarios. The other medications can be given in combination of two or more arbitrary.

Basándose en el mecanismo, los otros medicamentos que complementan y/o aumentan el efecto del compuesto de fórmula (I) para la prevención y/o tratamiento de trastornos incluyen no sólo medicamentos que ya se han encontrado, sino también los que se encontrarán en el futuro. Based on the mechanism, the other medications that complement and / or increase the effect of the compound of formula (I) for the prevention and / or treatment of disorders include not only drugs that have already been found, but also those that will be found in the future.

Para los fines descritos anteriormente, el compuesto de fórmula (I) de la presente invención, un éster alquílico del mismo o una sal no tóxica del mismo, o una combinación de ellos y otros medicamentos, puede administrarse normalmente de forma sistémica o parcial, normalmente por administración oral o parenteral. For the purposes described above, the compound of formula (I) of the present invention, an alkyl ester thereof or a non-toxic salt thereof, or a combination thereof and other medicaments, can usually be administered systemically or partially, usually by oral or parenteral administration.

Las dosificaciones se determinan dependiendo de la edad del paciente, el peso corporal, los síntomas, el efecto terapéutico deseado, la vía de administración y la duración del tratamiento, etc. En general, las dosis por persona y por administración para un ser humano adulto son de 1 a 100 mg hasta varias veces al día por administración oral. Como alternativa, son de 1 a 100 mg hasta varias veces al día por administración parenteral (preferiblemente en vena). O se administran en una vena de forma continua durante 1 a 24 horas al día. Dosages are determined depending on the patient's age, body weight, symptoms, desired therapeutic effect, route of administration and duration of treatment, etc. In general, the doses per person and per administration for an adult human being are 1 to 100 mg up to several times a day by oral administration. Alternatively, they are 1 to 100 mg up to several times a day by parenteral administration (preferably in a vein). Or they are administered in a vein continuously for 1 to 24 hours a day.

Como se ha mencionado anteriormente, las dosis a usar dependen de varias condiciones. De esta forma, las dosis a administrar pueden ser menores que la dosis especificada anteriormente en algunos casos y algunas veces pueden ser algo superiores. As mentioned above, the doses to be used depend on several conditions. In this way, the doses to be administered may be less than the dose specified above in some cases and sometimes they may be somewhat higher.

El compuesto de fórmula (I) de la presente invención y una sal no tóxica del mismo o una combinación del compuesto de fórmula (I) y otros medicamentos puede administrarse en forma de, por ejemplo, composiciones sólidas, composiciones líquidas u otras composiciones para administración oral, o como inyecciones, medicinas externas o supositorios, etc. para administración parenteral. The compound of formula (I) of the present invention and a non-toxic salt thereof or a combination of the compound of formula (I) and other medicaments can be administered in the form of, for example, solid compositions, liquid compositions or other compositions for administration. oral, or as injections, external medicines or suppositories, etc. for parenteral administration.

Las composiciones sólidas para administración oral incluyen comprimidos, píldoras, cápsulas, polvos dispersables y gránulos, etc. Solid compositions for oral administration include tablets, pills, capsules, dispersible powders and granules, etc.

Las cápsulas incluyen cápsulas duras y cápsulas blandas. The capsules include hard capsules and soft capsules.

En dichas composiciones sólidas, uno o más de los compuestos activos se mezclan con al menos un diluyente inerte, por ejemplo, lactosa, manitol, glucosa, hidroxipropil celulosa, celulosa microcristalina, almidón, polivinilpirrolidona, aluminato de metasilicato de magnesio, etc. Dichas composiciones pueden contener otras sustancias distintas de un diluyente inerte, por ejemplo, agentes lubricantes, por ejemplo, estearato de magnesio, agentes disgregantes, por ejemplo glicolato cálcico de celulosa, agentes para estabilizar, por ejemplo, lactosa, agentes auxiliares para la disolución, por ejemplo, ácido glutámico y ácido asparagínico. Los comprimidos o píldoras, si se desea, pueden recubrirse con películas gástricas o entéricas tales como azúcar, gelatina, hidroxipropil celulosa In said solid compositions, one or more of the active compounds are mixed with at least one inert diluent, for example, lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium metasilicate aluminate, etc. Such compositions may contain substances other than an inert diluent, for example, lubricating agents, for example, magnesium stearate, disintegrating agents, for example calcium cellulose glycolate, agents for stabilizing, for example, lactose, auxiliary agents for dissolution, for example, glutamic acid and asparagine acid. The tablets or pills, if desired, can be coated with gastric or enteric films such as sugar, gelatin, hydroxypropyl cellulose

o ftalato de hidroxipropilmetilcelulosa, etc., o recubrirse con dos o más películas. Y además, las composiciones también incluyen cápsulas de materiales absorbibles tales como gelatina. or hydroxypropyl methylcellulose phthalate, etc., or coated with two or more films. And in addition, the compositions also include capsules of absorbable materials such as gelatin.

Las composiciones líquidas para administración oral incluyen emulsiones, soluciones, jarabes y elixires farmacéuticamente aceptables, etc. En dichas composiciones líquidas, uno o más compuestos activos están incluidos en un diluyente inerte como los usados comúnmente en la técnica (por ejemplo, agua purificada, etanol). Además de diluyentes inertes, dichas composiciones también pueden comprender adyuvantes tales como agentes Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs, etc. In said liquid compositions, one or more active compounds are included in an inert diluent such as those commonly used in the art (eg, purified water, ethanol). In addition to inert diluents, said compositions may also comprise adjuvants such as agents

5 humectantes, agentes de suspensión, agentes edulcorantes, agentes aromatizantes, agentes de perfume y agentes conservantes. 5 humectants, suspending agents, sweetening agents, flavoring agents, perfume agents and preservatives.

Otras composiciones para administración oral incluyen composiciones de pulverización que pueden prepararse por métodos conocidos per se y que comprenden uno o más de los compuestos activos. Las composiciones de pulverización pueden comprender sustancias adicionales distintas de diluyentes inertes: por ejemplo, agentes estabilizantes tales como hidrógeno sulfato sódico, agentes estabilizantes para proporcionar isotonicidad al compuesto de título, tampón isotónico tal como cloruro sódico, citrato sódico y ácido cítrico. Para la preparación de dichas composiciones de pulverización, por ejemplo, puede usarse el método descrito en las Patentes de Estados Unidos Nº 2868691 o 3095355. Other compositions for oral administration include spray compositions that can be prepared by methods known per se and comprising one or more of the active compounds. The spray compositions may comprise additional substances other than inert diluents: for example, stabilizing agents such as sodium hydrogen sulfate, stabilizing agents for providing isotonicity to the title compound, isotonic buffer such as sodium chloride, sodium citrate and citric acid. For the preparation of said spray compositions, for example, the method described in US Pat. Nos. 2868691 or 3095355 can be used.

15 Las inyecciones para administración parenteral incluyen soluciones, suspensiones y emulsiones acuosas o no acuosas estériles. Las soluciones o suspensiones acuosas incluyen, por ejemplo, agua destilada para inyección y solución salina fisiológica. Las soluciones o suspensiones no acuosas incluyen, por ejemplo, propilenglicol, polietilenglicol, aceites vegetales tales como aceite de oliva, alcoholes tales como etanol, POLYSORBATE80 (marca comercial registrada), etc. Puede usarse mezclando soluciones, suspensiones y emulsiones acuosas o no acuosas estériles. Dichas composiciones pueden comprender diluyentes adicionales: por ejemplo agentes conservantes, agentes humectantes, agentes emulsionantes, agentes de dispersión, agentes estabilizantes (por ejemplo, lactosa), agentes auxiliares tales como agentes auxiliares para la disolución (por ejemplo, ácido glutámico y ácido asparagínico). Pueden esterilizarse, por ejemplo, por filtración a través de un filtro de retención de bacterias, por Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solutions or suspensions include, for example, distilled water for injection and physiological saline. Non-aqueous solutions or suspensions include, for example, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, POLYSORBATE80 (registered trademark), etc. It can be used by mixing sterile aqueous or non-aqueous solutions, suspensions and emulsions. Such compositions may comprise additional diluents: for example preservatives, wetting agents, emulsifying agents, dispersing agents, stabilizing agents (for example, lactose), auxiliary agents such as auxiliary agents for dissolution (for example, glutamic acid and asparagine acid) . They can be sterilized, for example, by filtration through a bacteria retention filter, by

25 incorporación de agentes de esterilización en las composiciones o por irradiación. También pueden fabricarse en forma de composiciones sólidas estériles (por ejemplo, las composiciones liofilizadas) y que pueden disolverse en agua estéril o algún otro diluyente estéril para la inyección inmediatamente antes del uso. Incorporation of sterilizing agents in the compositions or by irradiation. They can also be manufactured in the form of sterile solid compositions (for example, lyophilized compositions) and which can be dissolved in sterile water or some other sterile diluent for injection immediately before use.

Otras composiciones para administración parenteral incluyen líquidos para uso externo, y linimentos endémicos, pomadas, supositorios y supositorios vaginales que comprenden uno o más de los compuestos activos y pueden prepararse por métodos conocidos. Other compositions for parenteral administration include liquids for external use, and endemic liniments, ointments, suppositories and vaginal suppositories comprising one or more of the active compounds and can be prepared by known methods.

Best way to carry out the invention

35 Los siguientes ejemplos de referencia y Ejemplos pretenden ilustrar, pero no se limitan a, la presente invención. The following reference examples and Examples are intended to illustrate, but are not limited to, the present invention.

Los disolventes entre paréntesis en la sección de separaciones cromatográficas muestran el desarrollo disolventes de elusión y las proporciones de los disolventes usados se indican en volumen. Sin explicación especial, los datos de RMN se determinaron en una solución de CDCI3. Y los disolventes entre paréntesis en la sección de datos de RMN muestran los disolventes utilizados en la determinación. The solvents in parentheses in the chromatographic separations section show the development of elution solvents and the proportions of the solvents used are indicated by volume. Without special explanation, the NMR data was determined in a CDCI3 solution. And the solvents in brackets in the NMR data section show the solvents used in the determination.

Ejemplo de Referencia 1 Reference Example 1

Éster metílico del ácido 4-(2-nitro-4,5-dimetilfenoximetil)-3-metilbenzoico 45 4- (2-Nitro-4,5-dimethylphenoxymethyl) -3-methylbenzoic acid methyl ester

En una atmósfera de argón, una mezcla de 2-nitro-4,5-dimetilfenol (4 g), DMF (100 ml), se agitaron carbonato potásico (6,6 g) y éster metílico del ácido 4-mesiloximetil-3-metilbenzoico (6,8 g) durante 15 minutos a 60 ºC. Después de que se completara la reacción, la mezcla se enfrió y se vertió en agua helada. La mezcla se extrajo con acetato de etilo-hexano. La fase orgánica se lavó, se secó y se concentró a presión reducida para dar el compuesto del título (7,22 g) que tenía los siguientes datos físicos. Under an argon atmosphere, a mixture of 2-nitro-4,5-dimethylphenol (4 g), DMF (100 ml), potassium carbonate (6.6 g) and 4-mesyloxymethyl-3- acid methyl ester were stirred methylbenzoic acid (6.8 g) for 15 minutes at 60 ° C. After the reaction was complete, the mixture was cooled and poured into ice water. The mixture was extracted with ethyl acetate-hexane. The organic phase was washed, dried and concentrated under reduced pressure to give the title compound (7.22 g) having the following physical data.

TLC: Fr 0,24 (n-hexano:acetato de etilo = 4:1). TLC: Rf 0.24 (n-hexane: ethyl acetate = 4: 1).

Ejemplo de Referencia 2Éster metílico del ácido 4-(2-amino-4,5-dimetilfenoximetil)-3-metilbenzoico Reference Example 2 4- (2-Amino-4,5-dimethylphenoxymethyl) -3-methylbenzoic acid methyl ester

5 Una mezcla de éster metílico del ácido 4-(2-nitro-4,5-dimetilfenoximetil)-3-metilbenzoico preparada en el Ejemplo de Referencia 1 (7,21 g), ácido acético (88 ml) y agua (8,8 ml) se agitó a 50 ºC. A la solución de reacción, se le añadió gradualmente polvo de hierro (6,11 g) y la mezcla se agitó durante 1 hora a 50 ºC. Después de un periodo de refrigeración, la mezcla se filtró y el filtrado se concentró y se destiló azeotrópicamente con tolueno. Al residuo, se le A mixture of 4- (2-nitro-4,5-dimethylphenoxymethyl) -3-methylbenzoic acid methyl ester prepared in Reference Example 1 (7.21 g), acetic acid (88 ml) and water (8, 8 ml) was stirred at 50 ° C. To the reaction solution, iron powder (6.11 g) was gradually added and the mixture was stirred for 1 hour at 50 ° C. After a period of cooling, the mixture was filtered and the filtrate was concentrated and azeotropically distilled with toluene. The residue is given

10 añadieron acetato de etilo-agua (100 ml-100 ml) y la mezcla se filtró sobre Celite (marca registrada). La fase orgánica se lavó, se secó y se concentró a presión reducida para dar el compuesto del título (4,66 g) que tenía los siguientes datos físicos. TLC: Fr 0,51 (n-hexano:acetato de etilo = 2:1). 10 added ethyl acetate-water (100 ml-100 ml) and the mixture was filtered over Celite (registered trademark). The organic phase was washed, dried and concentrated under reduced pressure to give the title compound (4.66 g) having the following physical data. TLC: Fr 0.51 (n-hexane: ethyl acetate = 2: 1).

Ejemplo de Referencia 315 Éster metílico del ácido 3-metil-4-[2-[N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Reference Example 315 3-Methyl-4- [2- [N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid methyl ester

Una solución de éster metílico del ácido 4-(2-amino-4,5-dimetilfenoximetil)-3-metilbenzoico preparada en el Ejemplo A solution of 4- (2-amino-4,5-dimethylphenoxymethyl) -3-methylbenzoic acid methyl ester prepared in the Example

20 de Referencia 2 (632 mg) en piridina (4 ml) se enfrió a 0 ºC, después se añadió gota a gota cloruro de 5-metilfuran-2sulfonilo (490 mg) a la misma. Después de que la solución se agitara durante 1 hora a temperatura ambiente, la mezcla de reacción se diluyó con acetato de etilo y se vertió en agua. La fase orgánica se lavó, se secó y se concentró a presión reducida. El residuo se lavó mediante un disolvente mixto de éter diisopropílico y hexano para dar el compuesto del título (875 mg) que tenía los siguientes datos físicos. Reference 20 (632 mg) in pyridine (4 ml) was cooled to 0 ° C, then 5-methylfuran-2sulfonyl chloride (490 mg) was added dropwise thereto. After the solution was stirred for 1 hour at room temperature, the reaction mixture was diluted with ethyl acetate and poured into water. The organic phase was washed, dried and concentrated under reduced pressure. The residue was washed by a mixed solvent of diisopropyl ether and hexane to give the title compound (875 mg) having the following physical data.

25 TLC: Fr 0,42 (n-hexano:acetato de etilo = 2:1). 25 TLC: Fr 0.42 (n-hexane: ethyl acetate = 2: 1).

Ejemplo 1Éster metílico del ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 30 Example 1 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid methyl ester

A una solución de éster metílico del ácido 3-metil-4-[2-[N-(5-metil-2-furilsulfonil)amino]-4,5dimetilfenoximetil]benzoico preparada en el Ejemplo de Referencia 3 (870 mg) en N,N-dimetilacetamida (2 ml), se le To a solution of 3-methyl-4- [2- [N- (5-methyl-2-furylsulfonyl) amino] -4,5dimethylphenoxymethyl] benzoic acid methyl ester prepared in Reference Example 3 (870 mg) in N , N-dimethylacetamide (2 ml), it will be

35 añadieron carbonato de cesio (1,37 g) y yoduro de isobutilo (0,36 ml), y la mezcla se agitó durante 1 hora a 100 ºC. La mezcla de reacción se dejó enfriar y se vertió en acetato de etilo-agua (40 ml-40 ml). La fase orgánica se lavó, se secó y se concentró a presión reducida. El residuo se purificó por cromatografía en columna sobre gel de sílice (tolueno-acetato de etilo), dando el compuesto del título (855 mg) que tenía los siguientes datos físicos. TLC: Fr 0,51 (n-hexano:acetato de etilo = 2:1); 35 added cesium carbonate (1.37 g) and isobutyl iodide (0.36 ml), and the mixture was stirred for 1 hour at 100 ° C. The reaction mixture was allowed to cool and was poured into ethyl acetate-water (40 ml-40 ml). The organic phase was washed, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (toluene-ethyl acetate), to give the title compound (855 mg) which had the following physical data. TLC: Fr 0.51 (n-hexane: ethyl acetate = 2: 1);

40 RMN: δ 7,87 (d, J = 8,4 Hz, 1H), 7,86 (s, 1H), 7, 38 (d, J = 8,4 Hz, 1H), 7,04 (s, 1H), 6,70 (m, 2H), 5,93 (m, 1H), 4,91 (s a, 2H), 3,92 (s, 3H), 3,48 (m, 2H), 2,34 (s, 3H), 2,23 (s, 3H), 2,18 (s, 3H), 2,09 (s, 3H), 0,90 (s a, 6H). 40 NMR: δ 7.87 (d, J = 8.4 Hz, 1H), 7.86 (s, 1H), 7, 38 (d, J = 8.4 Hz, 1H), 7.04 (s , 1H), 6.70 (m, 2H), 5.93 (m, 1H), 4.91 (sa, 2H), 3.92 (s, 3H), 3.48 (m, 2H), 2 , 34 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 2.09 (s, 3H), 0.90 (sa, 6H).

Ejemplo 2 Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

5 A una solución de éster metílico del ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5dimetilfenoximetil]benzoico preparada en el Ejemplo 1 (850 mg) en dioxano (10 ml), se le añadieron hidróxido sódico acuoso 2 N (2,5 ml) y metanol (4 ml) y la mezcla se agitó durante 30 horas a temperatura ambiente. A la mezcla, se le añadió ácido clorhídrico 2 N y después también se le añadió acetato de etilo-agua (30 ml-15 ml). La fase orgánica To a solution of 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5dimethylphenoxymethyl] benzoic acid methyl ester prepared in Example 1 (850 mg) ) in dioxane (10 ml), 2N aqueous sodium hydroxide (2.5 ml) and methanol (4 ml) were added and the mixture was stirred for 30 hours at room temperature. To the mixture, 2N hydrochloric acid was added and then ethyl acetate-water (30 ml-15 ml) was also added. The organic phase

10 se lavó, se secó y se concentró a presión reducida. El residuo se disolvió en etanol caliente (40 ml), se añadió mediante agua caliente (40 ml), y después se dejó enfriar. El precipitado se filtró y se secó para dar el compuesto del título (755 mg) que tenía los siguientes datos físicos. TLC: Fr 0,78 (cloroformo: metanol: agua = 8:2: 0,2); RMN: δ 7,94 (d, J = 7,8 Hz, 1H), 7,93 (s, 1H), 7,44 (d, J = 7,8 Hz, 1H), 7,04 (s, 1H), 6,74-6,70 (m, 2H), 5,94 (dd, J = 10 was washed, dried and concentrated under reduced pressure. The residue was dissolved in hot ethanol (40 ml), added by hot water (40 ml), and then allowed to cool. The precipitate was filtered and dried to give the title compound (755 mg) which had the following physical data. TLC: Fr 0.78 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 7.94 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.04 (s, 1H), 6.74-6.70 (m, 2H), 5.94 (dd, J =

15 3,3, 0,9 Hz, 1H), 4,94 (a, 2H), 3,48 (d, J = 6,6 Hz, 2H), 2,37 (s, 3H), 2,24 (s, 3 H), 2,19 (s, 3H), 2,11 (s, 3H), 1,68 (sep, J = 6,6 Hz, 1H), 0,91 (d, J = 6,6 Hz, 6H). 15 3.3, 0.9 Hz, 1H), 4.94 (a, 2H), 3.48 (d, J = 6.6 Hz, 2H), 2.37 (s, 3H), 2.24 (s, 3 H), 2.19 (s, 3H), 2.11 (s, 3H), 1.68 (Sep, J = 6.6 Hz, 1H), 0.91 (d, J = 6 , 6 Hz, 6H).

Mediante los mismos procedimientos que se han descrito en los Ejemplos de Referencia 1 a 3 y Ejemplos 1 y 2, usando los compuestos correspondientes, se obtuvieron los compuestos del título que tienen los siguientes datos 20 físicos. By the same procedures as described in Reference Examples 1 to 3 and Examples 1 and 2, using the corresponding compounds, the title compounds having the following physical data were obtained.

Ejemplo 2(4) Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (4) 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

TLC: Fr 0,30 (cloroformo:metanol = 9:1); RMN: δ 8,12 y 7,46 (cada d, J = 8,1 Hz, cada 2H), 7,20 (s, 1H), 6,81 -6,75 (m, 2H), 6,01 -5,98 (m, 1H), 5,12-4,98 (m, 2H), 3,45 (d, J = 7,5 Hz, 2H), 2,34 y 2,19 (cada s, cada 3H), 1,75-1,59 (m, 1H), 0,91 (d, J = 6,9 Hz, 6H). TLC: Fr 0.30 (chloroform: methanol = 9: 1); NMR: δ 8.12 and 7.46 (every d, J = 8.1 Hz, every 2H), 7.20 (s, 1H), 6.81 -6.75 (m, 2H), 6.01 -5.98 (m, 1H), 5.12-4.98 (m, 2H), 3.45 (d, J = 7.5 Hz, 2H), 2.34 and 2.19 (each s, every 3H), 1.75-1.59 (m, 1H), 0.91 (d, J = 6.9 Hz, 6H).

Ejemplo 2(5) Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (5) 4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,38 (cloroformo:metanol = 10:1); RMN: δ 8,12-8,09 (m, 2H), 7,56 (d, J = 8,4 Hz, 2H), 6,81 (s, 1H), 6,79 (d, J = 3,3 Hz, 1H), 6,75 (s, 1H), 6,02 (dd, J = 3,3, 1,2 Hz, 1H), 5,10 (s, 2H), 4,48 (m, 1H),2,30 (s, 3H), 2,23 (s, 3H), 2,17 (s, 3H), 1,11 (d, J = 6,6 Hz, 6H). TLC: Fr 0.38 (chloroform: methanol = 10: 1); NMR: δ 8.12-8.09 (m, 2H), 7.56 (d, J = 8.4 Hz, 2H), 6.81 (s, 1H), 6.79 (d, J = 3 , 3 Hz, 1H), 6.75 (s, 1H), 6.02 (dd, J = 3.3, 1.2 Hz, 1H), 5.10 (s, 2H), 4.48 (m, 1H), 2.30 (s, 3H), 2.23 (s, 3H), 2, 17 (s, 3H), 1.11 (d, J = 6.6 Hz, 6H).

Ejemplo 2(6) Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (6) 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

5 TLC: Fr 0,38 (cloroformo:metanol = 10:1); RMN: δ 8,12-8,08 (m, 2H), 7,42 (d, J = 8,4 Hz, 2H), 7,03 (s, 1H), 6,71 (d, J = 3,3 Hz, 1H), 6,68 (s, 1H), 5,92 (dd, J = 3,3, 0,9 Hz, 1H), 5,00 (s a, 2H), 3,52-3,46 (m, 2H), 2,22 (s, 3H), 2,18 (s, 3H), 2,13 (s, 3H), 1,68 (m, 1H), 0,91 (d, J = 6,6 Hz, 6H). 5 TLC: Fr 0.38 (chloroform: methanol = 10: 1); NMR: δ 8.12-8.08 (m, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.03 (s, 1H), 6.71 (d, J = 3 , 3 Hz, 1H), 6.68 (s, 1H), 5.92 (dd, J = 3.3, 0.9 Hz, 1H), 5.00 (sa, 2H), 3.52-3 , 46 (m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 2.13 (s, 3H), 1.68 (m, 1H), 0.91 (d, J = 6.6 Hz, 6H).

10 Ejemplo 2(7)Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (7) 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

15 TLC: Fr 0,42 (cloroformo:metanol = 9:1); RMN: δ 8,00-7,89 (m, 2H), 7,41 (d, J = 8,4 Hz, 1H), 7,16 (s, 1H), 6,95 (s, 1H), 6,74 (d, J = 3,3 Hz, 1H), 5,96 (m, 1H), 4,94 (s, 2H), 3,47 (d, J = 6,3 Hz, 2H), 2,37 (s, 3H), 2,30 (s, 3H), 2,11 (s, 3H), 1,64 (m, 1H), 0,90 (d, J = 6,6 Hz, 6H). TLC: Fr 0.42 (chloroform: methanol = 9: 1); NMR: δ 8.00-7.89 (m, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.16 (s, 1H), 6.95 (s, 1H), 6.74 (d, J = 3.3 Hz, 1H), 5.96 (m, 1H), 4.94 (s, 2H), 3.47 (d, J = 6.3 Hz, 2H), 2.37 (s, 3H), 2.30 (s, 3H), 2.11 (s, 3H), 1.64 (m, 1H), 0.90 (d, J = 6.6 Hz, 6H ).

20 Ejemplo 2(8) Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (8) 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

25 TLC: Fr 0,58 (cloroformo:metanol = 9:1); RMN: δ 7,96 (d, J = 7,5 Hz, 1H), 7,94 (s, 1H), 7,47 (d, J = 7,5 Hz, 1H), 7,20 (s, 1H), 6,81 (s, 1H), 6,77 (d, J = 3,3 Hz, 1H), 6,03-5,97 (m, 1H), 4,99 (s a, 2H), 3,44 (d, J = 7,5 Hz, 2H), 2,39 (s, 3H), 2,36 (s, 3H), 2,17 (s, 3H), 1,75-1,60 (m, 1H), 0,89 (d, J = 6,6 Hz, 6H). 25 TLC: Fr 0.58 (chloroform: methanol = 9: 1); NMR: δ 7.96 (d, J = 7.5 Hz, 1H), 7.94 (s, 1H), 7.47 (d, J = 7.5 Hz, 1H), 7.20 (s, 1H), 6.81 (s, 1H), 6.77 (d, J = 3.3 Hz, 1H), 6.03-5.97 (m, 1H), 4.99 (sa, 2H), 3.44 (d, J = 7.5 Hz, 2H), 2.39 (s, 3H), 2.36 (s, 3H), 2.17 (s, 3H), 1.75-1.60 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H).

30 Ejemplo 2(9) Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (9) 3-Chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,38 (cloroformo:metanol = 9:1); RMN: δ 8,13 (d, J = 1,5 Hz, 1H), 8,02 (dd, J = 8,4, 1,5 Hz, 1H), 7,58 (d, J = 8,4 Hz, 1H), 7,15 (s, 1H), 6,94 (s, 1H), 6,76 (d, J = 3,3 Hz, 1H), 5,98 (m, 1H), 5,25-4,90 (a, 2H), 3,48 (d, J = 6,6 Hz, 2H), 2,31 (s, 3H), 2,16 (s, 3H), 1,64 (m, 1H), 0,92 (d, J = 6,6 Hz, 6H). TLC: Fr 0.38 (chloroform: methanol = 9: 1); NMR: δ 8.13 (d, J = 1.5 Hz, 1H), 8.02 (dd, J = 8.4, 1.5 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.15 (s, 1H), 6.94 (s, 1H), 6.76 (d, J = 3.3 Hz, 1H), 5.98 (m, 1H), 5.25-4.90 (a, 2H), 3.48 (d, J = 6.6 Hz , 2H), 2.31 (s, 3H), 2.16 (s, 3H), 1.64 (m, 1H), 0.92 (d, J = 6.6 Hz, 6H).

Ejemplo 2(10) Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (10) 3-Chloro-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,38 (cloroformo:metanol = 9:1); RMN: δ 8,12 (d, J = 1,5 Hz, 1H), 8,07 (dd, J = 8,4, 1,5 Hz, 1H), 7,88 (d, J = 8,4 Hz, 1H), 6,99 (s, 1H), 6,95 (s, 1H), 6,85 (d, J = 3,3 Hz, 1H), 6,06 (m, 1H), 5,20 (d, J = 14,4 Hz, 1H), 5,15 (d, J = 14,4 Hz, 1H), 4,48 (m, 1H), 2,33 (s, 3H), TLC: Fr 0.38 (chloroform: methanol = 9: 1); NMR: δ 8.12 (d, J = 1.5 Hz, 1H), 8.07 (dd, J = 8.4, 1.5 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 6.85 (d, J = 3.3 Hz, 1H), 6.06 (m, 1H), 5.20 (d, J = 14.4 Hz, 1H), 5.15 (d, J = 14 , 4 Hz, 1H), 4.48 (m, 1H), 2.33 (s, 3H),

15 2,30 (s, 3H), 1,11 (d, J = 6,3 Hz, 3H), 1,09 (d, J = 6,3 Hz, 3H). 15 2.30 (s, 3H), 1.11 (d, J = 6.3 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).

Ejemplo 2(11) Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (11) 3-Methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,49 (cloroformo:metanol = 9: 1); RMN: δ 7,78 (dd, J = 8,1, 1,5 Hz, 1H), 7,76 (d, J = 1,5 Hz, 1H), 7,59 (d, J = 1,5 Hz, 1H), 7,01 (s, 1H), 6,96 (s, 1H), 6,83 (d, J = 3,3 Hz, 1H), 6,05-6,00 (m, 1H), 5,11 (d, J = 14,1 Hz, 1H), 5,07 (d, J = 14,1 Hz, 1H), 4,55-4,40(m, 1H), TLC: Fr 0.49 (chloroform: methanol = 9: 1); NMR: δ 7.78 (dd, J = 8.1, 1.5 Hz, 1H), 7.76 (d, J = 1.5 Hz, 1H), 7.59 (d, J = 1.5 Hz, 1H), 7.01 (s, 1H), 6.96 (s, 1H), 6.83 (d, J = 3.3 Hz, 1H), 6.05-6.00 (m, 1H), 5.11 (d, J = 14.1 Hz, 1H), 5.07 (d , J = 14.1 Hz, 1H), 4.55-4.40 (m, 1H),

25 3,94 (s, 3H), 2,30 (s, 3H), 2,29 (s, 3H), 1,12 (d, J = 6,9 Hz, 6H). 25 3.94 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H), 1.12 (d, J = 6.9 Hz, 6H).

Ejemplo 2(12) Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (12) 3-Methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,44 (cloroformo:metanol = 9:1); RMN: δ 7,77 (dd, J = 8,1, 1,2 Hz, 1H), 7,74 (d, J = 8,1 Hz, 1H), 7,58 (d, J = 1,2 Hz, 1H), 6,84 (s, 1H), 6,81 (d, J = 3,3 Hz, 1H), 6,78 (s, 1H), 6,05-6,00 (m, 1H), 5,09 (s, 2H), 4,60-4,40 (m, 1H), 3,94 (s, 3H), 2,29 (s, 3H), 2,24 (s, 3H), 2,17 TLC: Fr 0.44 (chloroform: methanol = 9: 1); NMR: δ 7.77 (dd, J = 8.1, 1.2 Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.58 (d, J = 1.2 Hz, 1H), 6.84 (s, 1H), 6.81 (d, J = 3.3 Hz, 1H), 6.78 (s, 1H), 6.05-6.00 (m, 1H ), 5.09 (s, 2H), 4.60-4.40 (m, 1H), 3.94 (s, 3H), 2.29 (s, 3H), 2.24 (s, 3H) , 2.17

35 (s, 3H), 1,12 (d, J = 6,9 Hz, 6H). 35 (s, 3H), 1.12 (d, J = 6.9 Hz, 6H).

Ejemplo 2(13) Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (13) 3-Methoxy-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

5 TLC: Fr 0,45 (cloroformo:metanol = 9: 1); RMN: δ 7,73 (dd, J = 8,1, 1,2 Hz, 1H), 7,58 (d, J = 1,2 Hz, 1H), 7,40 (d, J = 8,1 Hz, 1H), 7,07 (s, 1H, 6,75-6,70 (m, 2H), 5,95-5,90 (m, 1H), 5,15-4,85 (m, 2H), 3,94 (s, 3H), 3,51 (a, 2H), 2,23 (s, 3H), 2,19 (s, 3H), 2,11 (s, 3H), 1,801,60 (m, 1H), 0,94 (a, 6H). 5 TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 7.73 (dd, J = 8.1, 1.2 Hz, 1H), 7.58 (d, J = 1.2 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.07 (s, 1H, 6.75-6.70 (m, 2H), 5.95-5.90 (m, 1H), 5.15-4.85 (m, 2H ), 3.94 (s, 3H), 3.51 (a, 2H), 2.23 (s, 3H), 2.19 (s, 3H), 2.11 (s, 3H), 1.801.60 (m, 1H), 0.94 (a, 6H).

10 Ejemplo 2(14)Ácido 2-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino-4-cloro-5-metilfenoximetil]benzoico Example 2 (14) 2-Methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino-4-chloro-5-methylphenoxymethyl] benzoic acid

15 TLC: Fr 0,46 (cloroformo:metanol =9:1); RMN (DMSO-d6): δ 13,02 (s, 1H), 7,58-7,50 (m, 3H), 7,24 (s, 1H), 6,98 (s, 1H), 6,94 (d, J = 3,3 Hz, 1H), 6,25 (m, 1H), 5,10 (d, J = 13,5 Hz, 1H), 5,04 (d, J = 13,5 Hz, 1H), 4,24 (m, 1H), 3,87 (s, 3H), 2,34 (s, 3H), 2,27 (s, 3H), 0,99 (d, J = 6,6 Hz, 3H), 0,98 (d, J = 6,6 Hz, 3H). TLC: Fr 0.46 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 13.02 (s, 1H), 7.58-7.50 (m, 3H), 7.24 (s, 1H), 6.98 (s, 1H), 6, 94 (d, J = 3.3 Hz, 1H), 6.25 (m, 1H), 5.10 (d, J = 13.5 Hz, 1H), 5.04 (d, J = 13.5 Hz, 1H), 4.24 (m, 1H), 3.87 (s, 3H), 2.34 (s, 3H), 2.27 (s, 3H), 0.99 (d, J = 6 , 6 Hz, 3H), 0.98 (d, J = 6.6 Hz, 3H).

20 Ejemplo 2(15)Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (15) 3-Chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

25 TLC: Fr 0,40 (cloroformo:metanol = 9:1); RMN: δ 8,12 (d, J = 1,8 Hz, 1H), 8,02 (dd, J = 8,1, 1,8 Hz, 1H), 7,61 (d, J = 8,1 Hz, 1H), 7,03 (s, 1H), 6,75 (d, J = 3,3 Hz, 1N), 6,70 (s, 1H), 5,96 (m, 1H), 5,25-4,85 (a, 2H), 3,50 (d, J = 6,6 Hz, 2H), 2,24 (s, 3H), 2,19 (s, 3H), 2,16 (s, 3H), 1,79 (m, 1H), 0,93 (d, J = 6,6 Hz, 6H). 25 TLC: Fr 0.40 (chloroform: methanol = 9: 1); NMR: δ 8.12 (d, J = 1.8 Hz, 1H), 8.02 (dd, J = 8.1, 1.8 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 6.75 (d, J = 3.3 Hz, 1N), 6.70 (s, 1H), 5.96 (m, 1H), 5, 25-4.85 (a, 2H), 3.50 (d, J = 6.6 Hz, 2H), 2.24 (s, 3H), 2.19 (s, 3H), 2.16 (s , 3H), 1.79 (m, 1H), 0.93 (d, J = 6.6 Hz, 6H).

30 Ejemplo 2(16)Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (16) 3-Chloro-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,39 (cloroformo:metanol = 9:1); RMN: δ 8,11 (d, J = 1,8 Hz, 1H), 8,06 (dd, J = 8,1, 1,8 Hz, 1H), 7,90 (d, J = 8,1 Hz, 1H), 6,86-6,80 (m, 2H), 6,75 (s, 1H), 6,05 (m, 1H), 5,17 (s, 2H), 4,51 (m, 1H), 2,32 (s, 3H), 2,25 (s, 3H), 2,18 (s, 3H), 1,12 (d, J = 6,6 Hz, 3H), 1,11 (d, J = 6,6 Hz, 3H). TLC: Fr 0.39 (chloroform: methanol = 9: 1); NMR: δ 8.11 (d, J = 1.8 Hz, 1H), 8.06 (dd, J = 8.1, 1.8 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 6.86-6.80 (m, 2H), 6.75 (s, 1H), 6.05 (m, 1H), 5.17 (s, 2H), 4.51 (m, 1H), 2.32 (s, 3H), 2.25 (s, 3H), 2, 18 (s, 3H), 1.12 (d, J = 6.6 Hz, 3H), 1.11 (d, J = 6.6 Hz, 3H).

Ejemplo 2(17) Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico Example 2 (17) 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid

10 TLC: Fr 0,37 (cloroformo:metanol = 9:1); RMN(CD3OD): δ 7,63 (d, J = 16,2 Hz, 1H), 7,45 (s) y 7,44 (d, J = 8,1 Hz) total 2H, 7,34(d, J =8,1 Hz, 1H), 7,17 (s, 1H), 7,10 (s, 1H), 6,72 (d, J = 3,3 Hz, 1H), 6,50 (d, J = 16,2 Hz, 1H), 6,08 (dd, J = 3,3, 1,2 Hz, 1H), 4,98 (s a, 2H), 3,44 (d, J = 6,9 Hz, 2H), 2,37 (s, 3H), 2,35 (s, 3H), 2,10 (s, 3H), 1,60 (m, 1H), 0,87 (d, J = 6,6 Hz, 6H). TLC: Fr 0.37 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 7.63 (d, J = 16.2 Hz, 1H), 7.45 (s) and 7.44 (d, J = 8.1 Hz) total 2H, 7.34 (d , J = 8.1 Hz, 1H), 7.17 (s, 1H), 7.10 (s, 1H), 6.72 (d, J = 3.3 Hz, 1H), 6.50 (d , J = 16.2 Hz, 1H), 6.08 (dd, J = 3.3, 1.2 Hz, 1H), 4.98 (sa, 2H), 3.44 (d, J = 6, 9 Hz, 2H), 2.37 (s, 3H), 2.35 (s, 3H), 2.10 (s, 3H), 1.60 (m, 1H), 0.87 (d, J = 6.6 Hz, 6H).

15 Ejemplo 2( 18)Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (18) 4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

20 TLC: Fr 0,31 (cloroformo:metanol =9:1); RMN: δ 7,73 (d, J = 15,9 Hz, 1H), 7,57 y 7,49 (cada d, J = 8,1 Hz, cada 2H), 6,98 y 6,92 (cada s, cada 1H), 6,81 (d, J = 3,3 Hz, 1H), 6,46 (d, J = 15,9 Hz, 1H), 6,03 (d, J = 3,3 Hz, 1H), 5,05 (s, 2H), 4,50-4,38 (m, 1H), 2,30 y 2,28 (cada s, cada 3H), 1,10 y 1,09 (cada d, J = 6,6 Hz, cada 3H). TLC: Fr 0.31 (chloroform: methanol = 9: 1); NMR: δ 7.73 (d, J = 15.9 Hz, 1H), 7.57 and 7.49 (each d, J = 8.1 Hz, every 2H), 6.98 and 6.92 (each s, every 1H), 6.81 (d, J = 3.3 Hz, 1H), 6.46 (d, J = 15.9 Hz, 1H), 6.03 (d, J = 3.3 Hz , 1H), 5.05 (s, 2H), 4.50-4.38 (m, 1H), 2.30 and 2.28 (each s, every 3H), 1.10 and 1.09 (each d, J = 6.6 Hz, every 3H).

25 Ejemplo 2(19)Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (19) 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

30 TLC: Fr 0,31 (cloroformo:metanol = 9:1); RMN: δ 7,77 (d, J = 15,9 Hz, 1H), 7,56 y 7,35 (cada d, J = 7,8 Hz, cada 2H), 7,14 y 6,92 (cada s, cada 1H), 6,72 (d, J = 3,6 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,95 (d, J = 3,6 Hz, 1H), 5,00-4,88 (m, 2H), 3,52-3,42 (m, 2H), 2,29 y 2,13 (cada s, cada 3H), 1,72-1,60 (m, 1H),0,90 (d, J = 6,3 Hz, 6H). TLC: Fr 0.31 (chloroform: methanol = 9: 1); NMR: δ 7.77 (d, J = 15.9 Hz, 1H), 7.56 and 7.35 (every d, J = 7.8 Hz, every 2H), 7.14 and 6.92 (each s, every 1H), 6.72 (d, J = 3.6 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H), 5.95 (d, J = 3.6 Hz , 1H), 5.00-4.88 (m, 2H), 3.52-3.42 (m, 2H), 2.29 and 2.13 (every s, every 3H), 1.72-1 , 60 (m, 1H), 0.90 (d, J = 6.3 Hz, 6H).

Ejemplo 2(20) Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (20) 4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

5 TLC: Fr 0,39 (cloroformo:metanol = 9:1); RMN: δ 7,78 (d, J = 15,9 Hz, 1H), 7,57 (d, J = 8,4 Hz, 2H), 7,50 (d, J = 8,4 Hz, 2H), 6,80 (s, 1H), 6,79 (d, J = 3,3 Hz, 1H), 6,76 (s, 1H), 6,46 (d, J = 15,9 Hz, 1H), 6,01 (m, 1H), 5,06 (s, 2H), 4,47 (sept, J = 6,6 Hz, 1H), 2,30 (s, 3H), 2,23 (s, 3H), 2,16 (s,3H), 1,11 y 1,10 (cada d, J = 6,6 Hz, cada 3H). 5 TLC: Fr 0.39 (chloroform: methanol = 9: 1); NMR: δ 7.78 (d, J = 15.9 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H) , 6.80 (s, 1H), 6.79 (d, J = 3.3 Hz, 1H), 6.76 (s, 1H), 6.46 (d, J = 15.9 Hz, 1H) , 6.01 (m, 1H), 5.06 (s, 2H), 4.47 (sept, J = 6.6 Hz, 1H), 2.30 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H), 1.11 and 1.10 (every d, J = 6.6 Hz, every 3H).

10 Ejemplo 2(22)Ácido 3-metil-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (22) 3-methyl-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

15 TLC: Fr 0,28 (n-hexano:acetato de etilo = 1:1); RMN: δ 7,97 (d, J = 7,8 Hz, 1H), 7,93 (s, 1H), 7,65 (d, J = 7,8 Hz, 1H), 6,82 (s, 1H), 6,79 (d, J = 3,3 Hz, 1H), 6,77 (s, 1H), 6,01 (dd, J = 3,3,1,2 Hz, 1H), 5,08 (d, J = 13,2 Hz, 1H), 5,02 (d, J = 13,2 Hz, 1H), 4,47 (quint, J = 6,6 Hz, 1H), 2,40 (s, 3H), 2,29 (s, 3H), 2,25 (s, 3H), 2,17 (s, 3H), 1,11 (d, J = 6,6 Hz, 6H). TLC: Fr 0.28 (n-hexane: ethyl acetate = 1: 1); NMR: δ 7.97 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.65 (d, J = 7.8 Hz, 1H), 6.82 (s, 1H), 6.79 (d, J = 3.3 Hz, 1H), 6.77 (s, 1H), 6.01 (dd, J = 3.3.1.2 Hz, 1H), 5, 08 (d, J = 13.2 Hz, 1H), 5.02 (d, J = 13.2 Hz, 1H), 4.47 (quint, J = 6.6 Hz, 1H), 2.40 ( s, 3H), 2.29 (s, 3H), 2.25 (s, 3H), 2.17 (s, 3H), 1.11 (d, J = 6.6 Hz, 6H).

20 Ejemplo 2(23)Ácido 3-metil-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (23) 3-methyl-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

25 TLC: Fr 0,30 (n-hexano:acetato de etilo = 1:2); EM (FAB, Pos.): 498 (M + H)+. TLC: Fr 0.30 (n-hexane: ethyl acetate = 1: 2); MS (FAB, Pos.): 498 (M + H) +.

Ejemplo 2(24)30 Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimedimetilfenoximetil]cinámico Example 2 (24) 30 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimedimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,26 (n-hexano:acetato de etilo = 1:2); 35 EM (FAB, Pos.): 512 (M + H)+. TLC: Rf 0.26 (n-hexane: ethyl acetate = 1: 2); 35 MS (FAB, Pos.): 512 (M + H) +.

Ejemplo 2(25) Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (25) 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

5 TLC: Fr 0,47 (cloroformo:metanol =9:1); RMN (DMSOd6): δ 7,69 (d, J = 8,1 Hz, 2H), 7,58 (d, J = 16,2 Hz, 1H), 7,34 (d, J = 8,1 Hz, 2H), 6,93 (s, 1H), 6,90 (s, 1H), 6,79 (d, J = 3,3 Hz, 1H), 6,54 (d, J = 16,2 Hz, 1H), 6,13 (m, 1H), 5,10-4,80 (m, 2H), 3,40-3,20 (m, 2H, cubierto con H2O en DMSO-d6), 2,18 (s, 3H), 2,11 (s, 3H), 2,10 (s, 3H), 1,58-1,42 (m, 1H), 0,82 (d, J = 6,6 Hz, 6H). 5 TLC: Fr 0.47 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.69 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 16.2 Hz, 1H), 7.34 (d, J = 8.1 Hz , 2H), 6.93 (s, 1H), 6.90 (s, 1H), 6.79 (d, J = 3.3 Hz, 1H), 6.54 (d, J = 16.2 Hz , 1H), 6.13 (m, 1H), 5.10-4.80 (m, 2H), 3.40-3.20 (m, 2H, covered with H2O in DMSO-d6), 2.18 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 1.58-1.42 (m, 1H), 0.82 (d, J = 6.6 Hz, 6H).

10 Ejemplo 2(26)Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (26) 3-Methoxy-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

15 TLC: Fr 0,30 (cloroformo:metanol = 9: 1); RMN: δ 7,76 (d, J = 15,9 Hz, 1H), 7,30 (d, J = 8,1 Hz, 1H), 7,26 (s, 1H), 7,20 (d, J = 8,1 Hz, 1H), 7,04 (s, 1H), 6,96 (s, 1H), 6,72 (d, J = 3,3 Hz, 1H), 6,46 (d, J = 15,9 Hz, 1H), 6,00-5,90 (m, 1H), 4,95 (s a, 2H), 3,91 (s, 3H), 3,48 (s a, 2H), 2,29 (s, 3H), 2,13 (s, 3H), 1,75-1,60 (m, 1H), 0,91 (d a, J = 6,6 Hz, 6H). TLC: Fr 0.30 (chloroform: methanol = 9: 1); NMR: δ 7.76 (d, J = 15.9 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.26 (s, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.96 (s, 1H), 6.72 (d, J = 3.3 Hz, 1H), 6.46 (d, J = 15.9 Hz, 1H), 6.00-5.90 (m, 1H), 4.95 (sa, 2H), 3.91 (s, 3H), 3.48 (sa, 2H), 2.29 (s, 3H), 2.13 (s, 3H), 1.75-1.60 (m, 1H), 0.91 (da, J = 6.6 Hz, 6H).

20 Ejemplo 2(27)Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (27) 4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

25 TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,11 (d, J = 8,1 Hz, 2H), 7,43 (d, J = 8,1 Hz, 2H), 7,12 (s, 1H), 6,77 (s, 1H), 6,73 (d, J = 3,3 Hz, 1H), 5,94 (m, 1H), 5,15-4,85 (a, 2H), 3,60-3,40 (a, 2H), 2,86 (t, J = 7,2 Hz, 4H), 2,14 (s, 3H), 2,13-2,00 (m, 2H), 1,68 (m, 1H), 1,020,82 (a, 6H). 25 TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.11 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.12 (s, 1H), 6.77 (s, 1H), 6.73 (d, J = 3.3 Hz, 1H), 5.94 (m, 1H), 5.15-4.85 (a, 2H), 3.60-3.40 (a , 2H), 2.86 (t, J = 7.2 Hz, 4H), 2.14 (s, 3H), 2.13-2.00 (m, 2H), 1.68 (m, 1H) , 1,020.82 (a, 6H).

30 Ejemplo 2(28) Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (28) 4- [6- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

35 TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,12 (d, J = 8,4 Hz, 2H), 7,57 (d, J = 8,4 Hz, 2H), 6,90 (s, 1H), 6,83 (s, 1H), 6,81 (d, J = 3,3 Hz, 1H), 6,02 (m, 1H), 5,17-5,05 (m, 2H), 4,49 (m, 1H), 2,93-2,79 (m, 4H), 2,31 (s, 3H), 2,15-2,00 (m, 2H), 1,12 (d, J = 6,6 Hz, 3H), 1,11 (d, J = 6,6 Hz, 3H). TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.12 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 6.90 (s, 1H), 6.83 (s, 1H), 6.81 (d, J = 3.3 Hz, 1H), 6.02 (m, 1H), 5.17-5.05 (m, 2H), 4.49 (m, 1H), 2.93-2.79 (m, 4H), 2.31 (s, 3H), 2.15-2.00 (m, 2H), 1.12 (d, J = 6.6 Hz, 3H) , 1.11 (d, J = 6.6 Hz, 3H).

Ejemplo 2(29) Ácido 4-[7-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-1,2,3,4-tetrahidronaftalen-6-iloximetil]benzoico Example 2 (29) 4- [7- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid

10 TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,10 (d, J = 8,1 Hz, 2H), 7,42 (d, J = 8,1 Hz, 2H), 6,95 (s, 1H), 6,73 (d, J = 3,3 Hz, 1H), 6,57 (s, 1H), 5,93 (m, 1H), 5,15-4,82 (a, 2H), 3,48 (d, J = 7,2 Hz, 2H), 2,77-2,60 (m, 4H), 2,13 (s, 3H), 1,82-1,60 (m, 5H), 0,92 (d, J = 6,6 Hz, 6H). 10 TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.10 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 6.95 (s, 1H), 6.73 (d, J = 3.3 Hz, 1H), 6.57 (s, 1H), 5.93 (m, 1H), 5.15-4.82 (a, 2H), 3.48 (d, J = 7 , 2 Hz, 2H), 2.77-2.60 (m, 4H), 2.13 (s, 3H), 1.82-1.60 (m, 5H), 0.92 (d, J = 6.6 Hz, 6H).

15 Ejemplo 2(30) Ácido 4-[7-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-1,2,3,4-tetrahidronaftalen-6-iloximetil]benzoico Example 2 (30) 4- [7- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid

20 TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,12 (d, J = 8,4 Hz, 2H), 7,56 (d, J = 8,4 Hz, 2H), 6,80 (d, J = 3,3 Hz, 1H), 6,74 (s, 1H), 6,64 (s, 1H), 6,02 (m, 1H), 5,16-5,04 (m, 2H), 4,48 (m, 1H), 2,77-2,58 (m, 4H), 2,30 (s, 3H), 1,82-1,69 (m, 4H), 1,12 (d, J = 6,6 Hz, 3H), 1,11 (d, J = 6,6 Hz, 3H). TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.12 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 3.3 Hz, 1H) , 6.74 (s, 1H), 6.64 (s, 1H), 6.02 (m, 1H), 5.16-5.04 (m, 2H), 4.48 (m, 1H), 2.77-2.58 (m, 4H), 2.30 (s, 3H), 1.82-1.69 (m, 4H), 1.12 (d, J = 6.6 Hz, 3H) , 1.11 (d, J = 6.6 Hz, 3H).

25 Ejemplo 2(31) Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (31) 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

30 TLC: Fr 0,30 (cloroformo:metanol =9:1), RMN(CD3OD) δ 7,65 (d, J = 15,9 Hz, 1H), 7,46 (s) y 7,44 (d, J = 7,8 Hz) total 2H, 7,34 (d, J = 7,8 Hz, 1H), 7,18 (s, 1H), 7,14 (s, 1H), 6,71 (d, J = 3,3 Hz, 1H), 6,50 (d, J = 15,9 Hz, 1H), 6,07 (dd, J = 3,3, 0,9 Hz, 1H), 4,95 (m, 2H), 3,44 (d, J = 7,5 Hz, 2H), 2,35 (s, 3H), 2,28 (s, 3H), 2,09 (s, 3H), 1,61 (m, 1H), 0,87 (d, J = 6,6 Hz, 6H). TLC: Fr 0.30 (chloroform: methanol = 9: 1), NMR (CD3OD) δ 7.65 (d, J = 15.9 Hz, 1H), 7.46 (s) and 7.44 (d , J = 7.8 Hz) total 2H, 7.34 (d, J = 7.8 Hz, 1H), 7.18 (s, 1H), 7.14 (s, 1H), 6.71 (d , J = 3.3 Hz, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.07 (dd, J = 3.3, 0.9 Hz, 1H), 4.95 (m, 2H), 3.44 (d, J = 7.5 Hz, 2H), 2.35 (s, 3H), 2.28 (s, 3H), 2.09 (s, 3H), 1 , 61 (m, 1H), 0.87 (d, J = 6.6 Hz, 6H).

Ejemplo 2(32) Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (32) 4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

5 TLC: Fr 0,42 (cloroformo:metanol = 9:1); RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,55 (d, J = 8,1 Hz, 2H), 7,37 (d, J = 8,1 Hz, 2H), 7,11 (s, 1H), 6,78 (s, 1H), 6,71 (d, J = 3,3 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,93 (m, 1H), 5,10-4,80 (a, 2H), 3,60-3,40 (a, 2H), 2,86 (t, J = 7,5 Hz, 4H), 2,14 (s, 3H), 2,08 (m, 2H), 1,68 (m, 1H), 1,00-0,82 (a, 6H). 5 TLC: Fr 0.42 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H) , 7.11 (s, 1H), 6.78 (s, 1H), 6.71 (d, J = 3.3 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H) , 5.93 (m, 1H), 5.10-4.80 (a, 2H), 3.60-3.40 (a, 2H), 2.86 (t, J = 7.5 Hz, 4H ), 2.14 (s, 3H), 2.08 (m, 2H), 1.68 (m, 1H), 1.00-0.82 (a, 6H).

10 Ejemplo 2(33)Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (33) 3-methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

15 TLC: Fr 0,3 3 (cloroformo:metanol = 10:1); RMN (CDCI3 + 1 gota de CD3OD) :δ 7,89 (d, J = 8,4 Hz, 1H), 7,88 (s, 1H), 7,39 (d, J = 8,4 Hz, 1H), 7,12 (s, 1H), 6,79 (s, 1H), 6,71 (d, J = 3,3 Hz, 1H), 5,94 (m, 1H), 5,06-4,74 (m, 2H), 3,60-3,37 (m, 2H), 2,92-2,82 (m, 4H), 2,34 (s, 3H), 2,17-2,03 (m, 2H), 2,10 (s, 3H), 1,69 (m, 1H), 1,01-0,80 (m, 6H). TLC: Fr 0.3 3 (chloroform: methanol = 10: 1); NMR (CDCI3 + 1 drop of CD3OD): δ 7.89 (d, J = 8.4 Hz, 1H), 7.88 (s, 1H), 7.39 (d, J = 8.4 Hz, 1H ), 7.12 (s, 1H), 6.79 (s, 1H), 6.71 (d, J = 3.3 Hz, 1H), 5.94 (m, 1H), 5.06-4 , 74 (m, 2H), 3.60-3.37 (m, 2H), 2.92-2.82 (m, 4H), 2.34 (s, 3H), 2.17-2.03 (m, 2H), 2.10 (s, 3H), 1.69 (m, 1H), 1.01-0.80 (m, 6H).

20 Ejemplo 2(34)Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (34) 3-methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

25 TLC: Fr 0,30 (cloroformo:metanol =10:1); RMN: δ 7,78 (d, J = 15,9 Hz, 1H), 7,42-7,36 (m, 3H), 7,10 (s, 1H), 6,80 (s, 1H), 6,72 (d, J = 3,3 Hz, 1H), 6,46 (d, J = 15,9 Hz, 1H), 5,94 (m, 1H), 5,04-4,77 (m, 2H), 3,59-3,37 (m, 2H), 2,91-2,82 (m, 4H), 2,34 (s, 3H), 2,14-2,05 (m, 2H), 2,12 (s, 3H), 1,68 (m, 1H),1,00-0,82 (m, 6H). 25 TLC: Fr 0.30 (chloroform: methanol = 10: 1); NMR: δ 7.78 (d, J = 15.9 Hz, 1H), 7.42-7.36 (m, 3H), 7.10 (s, 1H), 6.80 (s, 1H), 6.72 (d, J = 3.3 Hz, 1H), 6.46 (d, J = 15.9 Hz, 1H), 5.94 (m, 1H), 5.04-4.77 (m , 2H), 3.59-3.37 (m, 2H), 2.91-2.82 (m, 4H), 2.34 (s, 3H), 2.14-2.05 (m, 2H ), 2.12 (s, 3H), 1.68 (m, 1H), 1.00-0.82 (m, 6H).

Ejemplo 2(35) Ácido 4-[2-[N-(2-metil-2-propenil)-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (35) 4- [2- [N- (2-methyl-2-propenyl) -N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

5 TLC: Fr 0,42(cloroformo:metanol = 10:1); RMN: δ 8,11 (d, J = 8,1 Hz, 2H), 7,42 (d, J = 8,1 Hz, 2H), 7,02 (s, 1H), 6,74 (d, J = 3,3 Hz, 1H), 6,67 (s, 1H), 6,005,95 (m, 1H), 5,00 (s a, 2H), 4,77 (s, 2H), 4,26 (s a, 2H), 2,21 (s, 3H), 2,17 (s, 3H), 2,13 (s, 3H), 1,78 (s, 3H). 5 TLC: Fr 0.42 (chloroform: methanol = 10: 1); NMR: δ 8.11 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.02 (s, 1H), 6.74 (d, J = 3.3 Hz, 1H), 6.67 (s, 1H), 6.005.95 (m, 1H), 5.00 (sa, 2H), 4.77 (s, 2H), 4.26 ( sa, 2H), 2.21 (s, 3H), 2.17 (s, 3H), 2.13 (s, 3H), 1.78 (s, 3H).

10 Ejemplo 2(42) Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (42) 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

15 TLC: Fr 0,39 (cloroformo:metanol = 9:1); RMN: δ 8,13 (d, J = 8,1 Hz, 2H), 7,91 (d, J = 3,0 Hz, 1H), 7,52 (d, J = 8,1 Hz, 2H), 7,50 (d, J = 3,0 Hz, 1H), 7,10 (s, 1H), 6,85 (s, 1H), 5,09 (s, 2H), 4,67 (m, 1H), 2,36 (s, 3H), 1,16 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). TLC: Fr 0.39 (chloroform: methanol = 9: 1); NMR: δ 8.13 (d, J = 8.1 Hz, 2H), 7.91 (d, J = 3.0 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H) , 7.50 (d, J = 3.0 Hz, 1H), 7.10 (s, 1H), 6.85 (s, 1H), 5.09 (s, 2H), 4.67 (m, 1H), 2.36 (s, 3H), 1.16 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H).

Ejemplo 2(43)20 Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-dimetilfenoximetil]benzoico Example 2 (43) 20 4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,39 (cloroformo:metanol = 10:1); 25 RMN: δ 8,13 (d, J = 8,1 Hz, 2H), 7,52 (d, J = 8,1 Hz, 2H), 7,09 (s, 1H), 7,04 (m, 1H), 6,85 (s, 1H), 5,10 (s, 2H), 4,68 (m, 1H), 2,49 (d, J = 0,6 Hz, 3H), 2,36 (s, 3H), 1,15 (d, J = 6,6 Hz, 3H), 1,14 (d, J = 6,6 Hz, 3H). TLC: Fr 0.39 (chloroform: methanol = 10: 1); NMR: δ 8.13 (d, J = 8.1 Hz, 2H), 7.52 (d, J = 8.1 Hz, 2H), 7.09 (s, 1H), 7.04 (m , 1H), 6.85 (s, 1H), 5.10 (s, 2H), 4.68 (m, 1H), 2.49 (d, J = 0.6 Hz, 3H), 2.36 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H).

Ejemplo 2(44)Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico 30 Example 2 (44) 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid 30

TLC: Fr 0,40 (cloroformo:metanol =10:1); TLC: Fr 0.40 (chloroform: methanol = 10: 1);

RMN: δ 8,12 (d, J = 7,5 Hz, 2H), 7,37 (d, J = 7,5 Hz, 2H), 7,27 (d, J = 1,2 Hz, 1H), 6,96 (m, 1H), 6,78 (s, 1H), 5,1035 4,78 (m, 2H), 3,57 (s a, 2H), 2,35 (s, 3H), 2,34 (s, 3H), 1,70 (m, 1H), 0,94 (d, J = 6,6 Hz, 6H). NMR: δ 8.12 (d, J = 7.5 Hz, 2H), 7.37 (d, J = 7.5 Hz, 2H), 7.27 (d, J = 1.2 Hz, 1H) , 6.96 (m, 1H), 6.78 (s, 1H), 5.1035 4.78 (m, 2H), 3.57 (sa, 2H), 2.35 (s, 3H), 2 , 34 (s, 3H), 1.70 (m, 1H), 0.94 (d, J = 6.6 Hz, 6H).

Ejemplo 2(45) Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (45) 3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

5 TLC: Fr 0,69 (cloroformo:metanol:agua = 8:2: 0,2); RMN: δ 8,12 (d, J = 1,5 Hz, 1H), 8,06 (dd, J = 8,1, 1,5 Hz, 1H), 7,83 (d, J = 8,1 Hz, 1H), 7,11-7,10 (m, 2H), 6,86 (s, 1H), 5,23 (d, J = 14,4 Hz, 1H), 5,15 (d, J = 14,4 Hz, 1H), 4,71 (quint, J = 6,6 Hz, 1H), 2,52 (d, J = 1,2 Hz, 3H), 2,38 (s, 3H), 1,56 (d, J = 6,6 Hz, 3H), 1,34 (d, J = 6,6 Hz, 3H). 5 TLC: Fr 0.69 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 8.12 (d, J = 1.5 Hz, 1H), 8.06 (dd, J = 8.1, 1.5 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.11-7.10 (m, 2H), 6.86 (s, 1H), 5.23 (d, J = 14.4 Hz, 1H), 5.15 (d, J = 14.4 Hz, 1H), 4.71 (quint, J = 6.6 Hz, 1H), 2.52 (d, J = 1.2 Hz, 3H), 2.38 (s, 3H), 1.56 (d, J = 6.6 Hz, 3H), 1.34 (d, J = 6.6 Hz, 3H).

10 Ejemplo 2(47)Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (47) 3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

15 TLC: Fr 0,44 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,79 (s, 1H), 7,76 (d, J = 8,1 Hz, 1H). 7,56 (s, 1H), 7,29 (s, 1H), 7,27 (d, J = 8,1 Hz, 1H), 7,23 (s, 1H), 5,20-4,65 (m,2H), 3,55-3,35 (m, 2H), 2,36 (s, 3H), 2,31 (s, 3H), 2,21 (s, 3H), 1,65-1,47 (m, 1H), 0,84 (d, J = 6,6 Hz, 6H). TLC: Fr 0.44 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.79 (s, 1H), 7.76 (d, J = 8.1 Hz, 1H). 7.56 (s, 1H), 7.29 (s, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 5.20-4.65 (m, 2H), 3.55-3.35 (m, 2H), 2.36 (s, 3H), 2.31 (s, 3H), 2.21 (s, 3H), 1.65- 1.47 (m, 1H), 0.84 (d, J = 6.6 Hz, 6H).

20 Ejemplo 2(48)Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (48) 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

25 TLC: Fr 0,48 (cloroformo:metanol = 9:1); RMN: δ 7,74 (dd, J = 7,8, 1,2 Hz, 1H), 7,59 (d, J = 1,2 Hz, 1H), 7,31 (d, J = 7,8 Hz, 1H), 7,30 (s, 1H), 6,94 (s, 1H), 6,81 (s, 1H), 5,10-4,70 (m, 2H), 3,94 (s, 3H), 3,59 (a, 2H), 2,35 (s, 3H), 2,34 (s, 3H), 1,80-1,60 (m, 1H), 1,12 (d, J = 6,9 Hz, 6H). 25 TLC: Fr 0.48 (chloroform: methanol = 9: 1); NMR: δ 7.74 (dd, J = 7.8, 1.2 Hz, 1H), 7.59 (d, J = 1.2 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.30 (s, 1H), 6.94 (s, 1H), 6.81 (s, 1H), 5.10-4.70 (m, 2H), 3.94 (s , 3H), 3.59 (a, 2H), 2.35 (s, 3H), 2.34 (s, 3H), 1.80-1.60 (m, 1H), 1.12 (d, J = 6.9 Hz, 6H).

30 Ejemplo 2(50) Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (50) 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,38 (cloroformo:metanol = 9:1); RMN: δ 8,11 y 7,33 (cada d, J = 8,4 Hz, cada 2H), 7,22 (s, 1H), 6,92 y 6,91 (cada s, cada 1H), 5,10-4,70 (m, 2H), 3,74-3,42 (m, 2H), 2,31 y 2,30 (cada s, cada 3H), 1,78-1,62 (m, 1H), 1,05-0,83 (m, 6H). TLC: Fr 0.38 (chloroform: methanol = 9: 1); NMR: δ 8.11 and 7.33 (every d, J = 8.4 Hz, every 2H), 7.22 (s, 1H), 6.92 and 6.91 (every s, every 1H), 5 , 10-4.70 (m, 2H), 3.74-3.42 (m, 2H), 2.31 and 2.30 (every s, every 3H), 1.78-1.62 (m, 1H), 1.05-0.83 (m , 6H).

Ejemplo 2(51) Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (51) 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

10 TLC: Fr 0,28 (cloroformo:metanol = 9:1); RMN: δ 8,11 (s, 1H), 8,02 y 7,45 (cada d, J = 8,1 Hz, cada 1H), 7,21 (s, 1H), 6,97 (s, 1H), 6,94 (s, 1H), 5,12-4,74 (m, 2H), 3,75-3,45 (m, 2H), 2,32 y 2,31 (cada s, cada 3H), 1,80-1,62 (m, 1H), 1,05-0,82 (m, 6H). 10 TLC: Fr 0.28 (chloroform: methanol = 9: 1); NMR: δ 8.11 (s, 1H), 8.02 and 7.45 (every d, J = 8.1 Hz, every 1H), 7.21 (s, 1H), 6.97 (s, 1H ), 6.94 (s, 1H), 5.12-4.74 (m, 2H), 3.75-3.45 (m, 2H), 2.32 and 2.31 (every s, every 3H ), 1.80-1.62 (m, 1H), 1.05-0.82 (m, 6H).

Ejemplo 2(52)15 Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (52) 15-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,35 (cloroformo:metanol = 9: 1); RMN: δ 7,73 (d, J = 7,8 Hz, 1H), 7,59 (s, 1H), 7,30-7,20 (m, 2H), 6,95 (s, 1H), 6,91 (s, 1H), 5,09-4,62 (m, 2H), 3,94 20 (s, 3H), 3,78-3,45 (m, 2H), 2,31 (s, 6H), 1,79-1,63 (m, 1H), 1,08-0,85 (m, 6H). TLC: Fr 0.35 (chloroform: methanol = 9: 1); NMR: δ 7.73 (d, J = 7.8 Hz, 1H), 7.59 (s, 1H), 7.30-7.20 (m, 2H), 6.95 (s, 1H), 6.91 (s, 1H), 5.09-4.62 (m, 2H), 3.94 20 (s, 3H), 3.78-3.45 (m, 2H), 2.31 (s , 6H), 1.79-1.63 (m, 1H), 1.08-0.85 (m, 6H).

Ejemplo 2(53) Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (53) 3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,76 (cloroformo:metanol:agua = 8:2:0,2); RMN: δ 7,93 (d, J = 8,1 Hz, 1H), 7,92 (s, 1H), 7,30 (d, J = 8,1 Hz, 1H), 7,08 (s, 1H), 6,90 (d, J = 0,9 Hz, 1H), 6,71 (s, 1H), 4,91 (a, 1H), 4,79 (a, 1H), 3,65 (a, 1H), 3,56 (a, 1H), 2,35 (s, 3H), 2,30 (d, J = 0,9 Hz, 3H), 2,24 (s, 3H), 2,19 (s, TLC: Fr 0.76 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 7.93 (d, J = 8.1 Hz, 1H), 7.92 (s, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.90 (d, J = 0.9 Hz, 1H), 6.71 (s, 1H), 4.91 (a, 1H), 4.79 (a, 1H), 3.65 (a, 1H), 3.56 (a, 1H), 2.35 (s, 3H), 2, 30 (d, J = 0.9 Hz, 3H), 2.24 (s, 3H), 2.19 (s,

30 3H), 1,71 (sep, J = 6,9 Hz, 1H), 1,03-0,92 (a, 6H). 30 3H), 1.71 (Sep, J = 6.9 Hz, 1H), 1.03-0.92 (a, 6H).

Ejemplo 2(54) Ácido 3-metil-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (54) 3-methyl-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,78 (cloroformo:metanol:agua = 8:2: 0,2); RMN: δ 7,95 (d, J = 8,1 Hz, 1H), 7,93 (s, 1H), 7,54 (d, J = 8,1 Hz, 1H), 6,98 (d, J = 0,9 Hz, 1H), 6,86 (s, 1H), 6,78 (s, 1H), 5,03 (d, J = 13,2 Hz, 1H), 4,98 (d, J = 13,2 Hz, 1H), 4,69 (quint, J = 6,6 Hz, 1H), 2,46 (d, J = 0,9 Hz, 3H), 2,39 (s, 3H), 2,25 (s, 3H), 2,16 (s, 3H), 1,17 (d, J = 6,6 Hz, 3H), 1,13 (d, J = 6,6 Hz, 3H). TLC: Fr 0.78 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 7.95 (d, J = 8.1 Hz, 1H), 7.93 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 6.98 (d, J = 0.9 Hz, 1H), 6.86 (s, 1H), 6.78 (s, 1H), 5.03 (d, J = 13.2 Hz, 1H), 4.98 (d, J = 13.2 Hz, 1H), 4.69 (quint, J = 6.6 Hz, 1H) , 2.46 (d, J = 0.9 Hz, 3H), 2.39 (s, 3H), 2.25 (s, 3H), 2.16 (s, 3H), 1.17 (d, J = 6.6 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H).

Ejemplo 2(55) Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (55) 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,39 (cloroformo:metanol = 9:1); RMN: δ 7,72 (dd, J = 8,1, 1,2 Hz, 1H), 7,57 (d, J = 1,2 Hz, 1H), 7,26 (d, J = 8,1 Hz, 1H), 7,11 (s, 1H), 6,87 (s, 1H), 6,71 (s, 1H), 4,95 (a, 1H), 4,75 (a, 1H), 3,93 (s, 3H), 3,69 (a, 1H), 3,56 (a, 1H), 2,29 (s, 3H), 2,23 (s, 3H), 2,19 (s, 3H), TLC: Fr 0.39 (chloroform: methanol = 9: 1); NMR: δ 7.72 (dd, J = 8.1, 1.2 Hz, 1H), 7.57 (d, J = 1.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.11 (s, 1H), 6.87 (s, 1H), 6.71 (s, 1H), 4.95 (a, 1H), 4.75 (a, 1H), 3.93 (s, 3H), 3.69 (a, 1H), 3.56 (a , 1H), 2.29 (s, 3H), 2.23 (s, 3H), 2.19 (s, 3H),

15 1,80-1,65 (m, 1H), 0,97 (a, 6H). 15 1.80-1.65 (m, 1H), 0.97 (a, 6H).

Ejemplo 2(56) Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (56) 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,36 (cloroformo:metanol = 9:1); RMN: δ 8,11 (d, J = 1,8 Hz, 1H), 8,01 (dd, J = 8,1, 1,8 Hz, 1H), 7,49 (d, J = 8,1 Hz, 1H), 7,08 (s, 1H), 6,95 (d, J = 0,6 Hz, 1H), 6,69 (s, 1H), 5,20-4,70 (a, 2H), 3,80-3,45 (a, 2H), 2,32 (d, J = 0,6 Hz, 3H), 2,24 (s, 3H), 2,19 (s, 3H), 1,75 TLC: Fr 0.36 (chloroform: methanol = 9: 1); NMR: δ 8.11 (d, J = 1.8 Hz, 1H), 8.01 (dd, J = 8.1, 1.8 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.08 (s, 1H), 6.95 (d, J = 0.6 Hz, 1H), 6.69 (s, 1H), 5.20-4.70 (a, 2H ), 3.80-3.45 (a, 2H), 2.32 (d, J = 0.6 Hz, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 1 , 75

25 (m, 1H), 1,07-0,85 (a, 6H). 25 (m, 1H), 1.07-0.85 (a, 6H).

Ejemplo 2(57) Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (57) 3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,36 (cloroformo:metanol = 9: 1); RMN (CDCI3 + CD3OD): δ 8,06 (d, J = 1,8 Hz, 1H), 7,98 (dd, J = 8,1, 1,8 Hz, 1H), 7,70 (d, J = 8,1 Hz, 1H), 7,05 (d, J = 0,6 Hz, 1H), 6,86 (s, 1H), 6,76 (s, 1H), 5,14 (d, J = 14,1 Hz, 1H), 5,08 (d, J = 14,1 Hz, 1H), 4,70 (m, 1H), 2,47 (d, J TLC: Fr 0.36 (chloroform: methanol = 9: 1); NMR (CDCI3 + CD3OD): δ 8.06 (d, J = 1.8 Hz, 1H), 7.98 (dd, J = 8.1, 1.8 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.05 (d, J = 0.6 Hz, 1H), 6.86 (s, 1H), 6.76 (s, 1H), 5.14 (d, J = 14.1 Hz, 1H), 5.08 (d, J = 14.1 Hz, 1H), 4.70 (m, 1H), 2.47 (d, J

35 = 0,6 Hz, 3H), 2,25 (s, 3H), 2,17 (s, 3H), 1,17 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). 35 = 0.6 Hz, 3H), 2.25 (s, 3H), 2.17 (s, 3H), 1.17 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H).

Ejemplo 2(58) Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (58) 4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,45 (cloroformo:metanol = 10:1); RMN: δ 8,11 -8,08 (m, 2H), 7,49 (d, J = 8,4 Hz, 2H), 6,97 (d, J = 0,9 Hz, 1H), 6,86 (s, 1H), 6,75 (s, 1H), 5,06 (d, J = 5 12,9 Hz, 1H), 5,04 (d, J = 12,9 Hz, 1H), 4,71 (m, 1H), 2,46 (d, J = 0,9 Hz, 3H), 2,23 (s, 3H), 2,16 (s, 3H), 1,18 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). TLC: Fr 0.45 (chloroform: methanol = 10: 1); NMR: δ 8.11 -8.08 (m, 2H), 7.49 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 0.9 Hz, 1H), 6, 86 (s, 1H), 6.75 (s, 1H), 5.06 (d, J = 5 12.9 Hz, 1H), 5.04 (d, J = 12.9 Hz, 1H), 4 , 71 (m, 1H), 2.46 (d, J = 0.9 Hz, 3H), 2.23 (s, 3H), 2.16 (s, 3H), 1.18 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H).

Ejemplo 2(59)Example 2 (59)

Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 10 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid 10

TLC: Fr 0,43 (cloroformo:metanol = 10:1); TLC: Fr 0.43 (chloroform: methanol = 10: 1);

RMN: δ 8,09 (d, J = 8,1 Hz, 2H), 7,33 (d, J = 8,1 Hz, 2H), 7,08 (s, 1H), 6,89 (d, J = 0,9 Hz, 1H), 6,68 (s, 1H), 5,0815 4,68 (m, 2H), 3,75-3,45 (m, 2H), 2,30 (s, 3H), 2,23 (s, 3H), 2,18 (s, 3H), 1,71 (m, 1H), 1,04-0,83 (m, 6H). NMR: δ 8.09 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.08 (s, 1H), 6.89 (d, J = 0.9 Hz, 1H), 6.68 (s, 1H), 5.0815 4.68 (m, 2H), 3.75-3.45 (m, 2H), 2.30 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 1.71 (m, 1H), 1.04-0.83 (m, 6H).

Ejemplo 2(60)Example 2 (60)

Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid

TLC: Fr 0,22 (cloroformo:metanol = 9:1); RMN (CD3OD): δ 7,69 (d, J = 16,2 Hz, 1H), 7,61 (d, J = 8,1 Hz, 2H), 7,32-7,24 (m) y 7,29 (d, J = 8,1 Hz) total 4H, 7,05 (s, 1H), 6,52 (d, J = 16,2 Hz, 1H), 5,05-4,70 (m, 2H, cubierto con H2O en CD3OD), 3,63-3,50 (m, 2H), 2,37 (s, TLC: Fr 0.22 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 7.69 (d, J = 16.2 Hz, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.32-7.24 (m) and 7 , 29 (d, J = 8.1 Hz) total 4H, 7.05 (s, 1H), 6.52 (d, J = 16.2 Hz, 1H), 5.05-4.70 (m, 2H, covered with H2O in CD3OD), 3.63-3, 50 (m, 2H), 2.37 (s,

25 3H), 2,22 (d, J = 0,9 Hz, 3H), 1,65 (m, 1H), 0,93 (d, J = 6,3 Hz, 6H). 25 3H), 2.22 (d, J = 0.9 Hz, 3H), 1.65 (m, 1H), 0.93 (d, J = 6.3 Hz, 6H).

Ejemplo 2(63) Ácido 3-metil-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (63) 3-Methyl-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,20 (n-hexano:acetato de etilo = 1:2); EM (FAB, Pos.): 515(M + H)+. TLC: Fr 0.20 (n-hexane: ethyl acetate = 1: 2); MS (FAB, Pos.): 515 (M + H) +.

Ejemplo 2(64) Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (64) 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

5 TLC: Fr 0,22 (n-hexano:acetato de etilo = 1:2); EM (FAB, Pos.): 529 (M + H)+. 5 TLC: Rf 0.22 (n-hexane: ethyl acetate = 1: 2); MS (FAB, Pos.): 529 (M + H) +.

Ejemplo 2(65)10 Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (65) 10 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

TLC: Fr 0,31 (cloroformo:metanol = 9:1); 15 RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,56 y 7,27 (cada d, J = 8,1 Hz, cada 2H), 7,21 (s, 1H), 6,95-6,88 (m, 2H), 6,48 (d, J = 15,9 Hz, 1H), 5,00-4,65 (m, 2H), 3,72-3,42 (m, 2H), 2,33-2,22 (m, 6H), 1,78-1,60 (m, 1H), 1,05-0,83 (m, 6H). TLC: Fr 0.31 (chloroform: methanol = 9: 1); 15 NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.56 and 7.27 (every d, J = 8.1 Hz, every 2H), 7.21 (s, 1H) , 6.95-6.88 (m, 2H), 6.48 (d, J = 15.9 Hz, 1H), 5.00-4.65 (m, 2H), 3.72-3.42 (m, 2H), 2.33-2.22 (m, 6H), 1.78-1.60 (m, 1H), 1.05-0.83 (m, 6H).

Ejemplo 2(66)Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico 20 Example 2 (66) 3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

TLC: Fr 0,30 (cloroformo:metanol = 9:1); TLC: Fr 0.30 (chloroform: methanol = 9: 1);

RMN: δ 7,76 (d, J = 16,2 Hz, 1H), 7,42-7,37 (m, 2H), 7,30-7,15 (m, 2H), 6,98-6,89 (m, 2H), 6,47 (d, J = 16,2 Hz, 1H), 25 4,95-4,67 (m, 2H), 3,72-3,40 (m, 2H), 2,38-2,22 (m, 9H), 1,77-1,61 (m, 1H), 1,05-0,82 (m, 6H). NMR: δ 7.76 (d, J = 16.2 Hz, 1H), 7.42-7.37 (m, 2H), 7.30-7.15 (m, 2H), 6.98-6 , 89 (m, 2H), 6.47 (d, J = 16.2 Hz, 1H), 4.95-4.67 (m, 2H), 3.72-3.40 (m, 2H) , 2.38-2.22 (m, 9H), 1.77-1.61 (m, 1H), 1.05-0.82 (m, 6H).

Ejemplo 2(67)Example 2 (67)

Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid

TLC: Fr 0,41 (cloroformo:metanol = 9:1); RMN: δ 7,76 (d, J = 16,2 Hz, 1H), 7,39 (d, J = 8,4 Hz, 1H), 7,38 (s, 1H), 7,27 (d, J = 8,4 Hz, 1H), 7,23 (s, 1H), 6,97 (s, 1H), 6,81 (s, 1H), 6,47 (d, J = 16,2 Hz, 1H), 5,04-4,66 (m, 2H), 3,65-3,39 (m, 2H), 2,36 (s, 3H), 2,35 (s, 3H), 2,33 (s, TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR: δ 7.76 (d, J = 16.2 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.38 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.23 (s, 1H), 6.97 (s, 1H), 6.81 (s, 1H), 6.47 (d, J = 16.2 Hz, 1H), 5.04-4.66 (m, 2H), 3.65-3.39 (m , 2H), 2.36 (s, 3H), 2.35 (s, 3H), 2.33 (s,

3H), 1,75-1,61 (m, 1H), 0,92 (d, J = 6,6 Hz, 6H). 3H), 1.75-1.61 (m, 1H), 0.92 (d, J = 6.6 Hz, 6H).

Ejemplo 2(68) Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (68) 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,33 (cloroformo:metanol = 10:1); EM (APCI, Neg. 20V): 513 (M -H)-. TLC: Fr 0.33 (chloroform: methanol = 10: 1); MS (APCI, Neg. 20V): 513 (M-H) -.

Ejemplo 2(69) Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (69) 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

15 TLC: Fr 0,17 (cloroformo:metanol = 9:1); RMN (CD3OD): δ 7,69 (d, J = 1,8 Hz, 1H), 7,65 (d, J = 15,9 Hz, 1H), 7,59 (dd, J = 8,1, 1,5 Hz, 1H), 7,35 (d, J = 8,1 Hz, 1H), 7,29 (d, J = 1,2 Hz, 1H), 7,04 (s, 1H), 6,88 (s, 1H), 6,57 (d, J = 15,9 Hz, 1H), 5,10-4,60 (m, 2H), 3,63-3,50 (m, 2H), 2,28 (s, 3H), 2,21 (d, J = 1,2 Hz) y 2,20 (s) total 6H, 1,66 (m, 1H), 1,03-0,85 (m, 6H). TLC: Fr 0.17 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 7.69 (d, J = 1.8 Hz, 1H), 7.65 (d, J = 15.9 Hz, 1H), 7.59 (dd, J = 8.1, 1.5 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 1.2 Hz, 1H), 7.04 (s, 1H), 6 , 88 (s, 1H), 6.57 (d, J = 15.9 Hz, 1H), 5.10-4.60 (m, 2H), 3.63-3.50 (m, 2H), 2.28 (s, 3H), 2.21 (d, J = 1.2 Hz) and 2.20 (s) total 6H, 1.66 (m, 1H), 1.03-0.85 (m , 6H).

20 Ejemplo 2(70)Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (70) 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

25 TLC: Fr 0,40 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 545 (M + H)+. 25 TLC: Fr 0.40 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 545 (M + H) +.

Ejemplo 2(71)30 Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (71) 30 4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,43 (cloroformo:metanol = 9:1); RMN: δ 8,10 (d, J = 8,4 Hz, 2H), 7,34 (d, J = 8,4 Hz, 2H), 7,16 (s, 1H), 6,89 (d, J = 0,9 Hz, 1H), 6,76 (s, 1H), 5,064,70 (a, 2H), 3,78-3,45 (a, 2H), 2,87 (t, J = 7,5 Hz, 4H), 2,31 (d, J = 0,9 Hz, 3H), 2,09 (m, 2H), 1,74 (m, 1H), 1,04-0,86 (a, 6H). TLC: Fr 0.43 (chloroform: methanol = 9: 1); NMR: δ 8.10 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.16 (s, 1H), 6.89 (d, J = 0.9 Hz, 1H), 6.76 (s, 1H), 5,064.70 (a, 2H), 3.78-3.45 (a, 2H), 2.87 (t, J = 7 , 5 Hz, 4H), 2.31 (d, J = 0.9 Hz, 3H), 2.09 (m, 2H), 1.74 (m, 1H), 1.04-0.86 (a , 6H).

Ejemplo 2(72) Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (72) 4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

10 TLC: Fr 0,42 (cloroformo:metanol = 9:1); RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,55 (d, J = 8,1 Hz, 2H), 7,28 (d, J = 8,1 Hz, 2H), 7,15 (s, 1H), 6,89 (d, J = 0,9 Hz, 1H), 6,77 (s, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,05-4,60 (a, 2H), 3,78-3,45 (a, 2H), 2,86 (t, J = 7,8 Hz, 4H), 2,30 (d, J = 0,9 Hz, 3H), 2,08 (m, 2H), 1,73 (m, 1H), 1,06-0,83 (a, 6H). 10 TLC: Fr 0.42 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H) , 7.15 (s, 1H), 6.89 (d, J = 0.9 Hz, 1H), 6.77 (s, 1H), 6.47 (d, J = 15.9 Hz, 1H) , 5.05-4.60 (a, 2H), 3.78-3.45 (a, 2H), 2.86 (t, J = 7.8 Hz, 4H), 2.30 (d, J = 0.9 Hz, 3H), 2.08 (m, 2H), 1.73 (m, 1H), 1.06-0.83 (a, 6H).

15 Ejemplo 2(73) Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico. Example 2 (73) 3-methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid.

20 TLC: Fr 0,34 (diclorometano:metanol = 19:1); RMN: δ 7,95-7,92 (m, 2H), 7,31 (d, J = 7,8 Hz, 1H), 7,16 (s, 1H), 6,91 (s a, 1H), 6,79 (s, 1H), 4,93 (s a, 1H),4,73 (s a, 1H), 3,75-3,45 (m, 2H), 2,92-2,84 (m, 4H), 2,34 (s, 3H), 2,31 (d, J = 0,6 Hz, 3H), 2,10 (m, 2H), 1,74 (m, 1H), 1,080,80 (s a, 6H). TLC: Fr 0.34 (dichloromethane: methanol = 19: 1); NMR: δ 7.95-7.92 (m, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.16 (s, 1H), 6.91 (sa, 1H), 6.79 (s, 1H), 4.93 (sa, 1H), 4.73 (sa, 1H), 3.75-3.45 (m, 2H), 2.92-2.84 (m, 4H), 2.34 (s, 3H), 2.31 (d, J = 0.6 Hz, 3H), 2.10 (m, 2H), 1.74 (m, 1H), 1,080.80 ( sa, 6H).

25 Ejemplo 2(74) Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (74) 3-methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

30 TLC: Fr 0,32 (diclorometano:metanol = 19:1); RMN: δ 7,76 (d, J = 15,9 Hz, 1H), 7,40-7,36 (m, 2H), 7,25 (m, 1H), 7,14 (s, 1H), 6,91 (s a, 1H), 6,80 (s, 1H), 6,46 (d, J = 15,9 Hz, 1H), 4,90 (s a, 1H), 4,69 (s a, 1H), 3,75-3,43 (m, 2H), 2,95-2,80 (m, 4H), 2,31 (s, 6H), 2,09 (m, 2H), 1,72 (m, 1H), 1,05-0,85 (s a, 6H). TLC: Fr 0.32 (dichloromethane: methanol = 19: 1); NMR: δ 7.76 (d, J = 15.9 Hz, 1H), 7.40-7.36 (m, 2H), 7.25 (m, 1H), 7.14 (s, 1H), 6.91 (sa, 1H), 6.80 (s, 1H), 6.46 (d, J = 15.9 Hz, 1H), 4.90 (sa, 1H), 4.69 (sa, 1H ), 3.75-3.43 (m, 2H), 2.95-2.80 (m, 4H), 2.31 (s, 6H), 2.09 (m, 2H), 1.72 ( m, 1H), 1.05-0.85 (sa, 6H).

Ejemplo 2(77) Ácido 3-cloro-4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (77) 3-Chloro-4- [2- [N-isopropyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

5 TLC: Fr 0,43 (cloroformo:metanol = 9:1); RMN (CD3OD): δ 8,63 (m, 1H), 8,02 (d, J = 1,8 Hz, 1H), 7,98-7,84 (m, 3H), 7,70 (d, J = 8,1 Hz, 1H), 7,50 (m, 1H), 7,11 (s, 1H), 7,09 (s, 1H), 5,16 (Abd, J = 13,5 Hz) y 5,08 (Abd, J = 13,5 Hz) total 2H, 4,61 (sept, J = 6,6 Hz, 1H), 2,39 (3, 3H), 1,12 (d, J = 6,6 Hz) y 1,10 (d, J = 6,6 Hz) total 6H. 5 TLC: Fr 0.43 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 8.63 (m, 1H), 8.02 (d, J = 1.8 Hz, 1H), 7.98-7.84 (m, 3H), 7.70 (d, J = 8.1 Hz, 1H), 7.50 (m, 1H), 7.11 (s, 1H), 7.09 (s, 1H), 5.16 (Abd, J = 13.5 Hz) and 5.08 (Abd, J = 13.5 Hz) total 2H, 4.61 (sept, J = 6.6 Hz, 1H), 2.39 (3, 3H), 1.12 (d, J = 6.6 Hz) and 1.10 (d, J = 6.6 Hz) total 6H.

10 Ejemplo 2(78)Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (78) 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

15 TLC: Fr 0,37 (cloroformo:metanol = 10:1); RMN: δ 8,52 (m, 1H), 7,94-7,92 (m, 2H), 7,77-7,68 (m, 2H), 7,31-7,24 (m, 3H), 6,76 (s, 1H), 4,83 (s a, 2H), 3,65-3,50 (m, 2H), 2,34 (s, 6H), 1,66 (m, 1H), 0,91 (d, J = 6,6 Hz, 6H). TLC: Fr 0.37 (chloroform: methanol = 10: 1); NMR: δ 8.52 (m, 1H), 7.94-7.92 (m, 2H), 7.77-7.68 (m, 2H), 7.31-7.24 (m, 3H) , 6.76 (s, 1H), 4.83 (sa, 2H), 3.65-3.50 (m, 2H), 2.34 (s, 6H), 1.66 (m, 1H), 0.91 (d, J = 6.6 Hz, 6H).

20 Ejemplo 2(79) Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (79) 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid

25 TLC: Fr 0,16 (diclorometano:metanol = 20:1); RMN: δ 12,90 (s, 1H), 8,67 (d, J = 1,8 Hz, 1H), 8,62 (dd, J = 4,8, 1,8 Hz, 1H), 7,94 (dt, J = 8,1, 1,8 Hz, 1H), 7,74 (s, 1H), 7,68 (d, J = 8,1 Hz, 1H), 7,37 (dd, J = 8,1, 4,8 Hz, 1H), 7,27 (s, 1H), 7,24 (s, 1H), 7,01 (d, J = 8,1 Hz, 1H), 4,95 (a, 1H), 4,76 (a, 1H), 3,45-3,30 (m, 2H), 2,34 (s, 3H), 2,24 (s, 3H), 1,49 (sept, J = 6,6 Hz, 1H), 0,90-0,70 (a, 6H). 25 TLC: Rf 0.16 (dichloromethane: methanol = 20: 1); NMR: δ 12.90 (s, 1H), 8.67 (d, J = 1.8 Hz, 1H), 8.62 (dd, J = 4.8, 1.8 Hz, 1H), 7, 94 (dt, J = 8.1, 1.8 Hz, 1H), 7.74 (s, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.37 (dd, J = 8.1, 4.8 Hz, 1H), 7.27 (s, 1H), 7.24 (s, 1H), 7.01 (d, J = 8.1 Hz, 1H), 4.95 (a, 1H), 4.76 (a, 1H), 3.45-3.30 (m, 2H), 2.34 (s, 3H), 2.24 (s, 3H), 1.49 ( sept, J = 6.6 Hz, 1H), 0.90-0.70 (a, 6H).

30 Ejemplo 2(80) Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (80) 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

35 TLC: Fr 0,40 (cloroformo:metanol = 9:1); RMN: δ 8,50-8,40 (m, 1H), 7,95-7,85 (m, 2H), 7,75-7,60 (m, 2H), 7,30-7,20 (m, 3H), 6,89 (s, 1H), 4,76 (a, 2H), 3,61 TLC: Fr 0.40 (chloroform: methanol = 9: 1); NMR: δ 8.50-8.40 (m, 1H), 7.95-7.85 (m, 2H), 7.75-7.60 (m, 2H), 7.30-7.20 ( m, 3H), 6.89 (s, 1H), 4.76 (a, 2H), 3.61

(a, 2H), 2,31 (s, 3H), 2,29 (s, 3H), 1,75-1,55 (m, 1H), 1,00-0,80 (m, 6H). (a, 2H), 2.31 (s, 3H), 2.29 (s, 3H), 1.75-1.55 (m, 1H), 1.00-0.80 (m, 6H).

Ejemplo 2(81) Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (81) 4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

TLC: Fr 0,31 (cloroformo:metanol = 9:1); TLC: Fr 0.31 (chloroform: methanol = 9: 1);

RMN: δ 8,83 (d, J = 2,4, 0,6 Hz, 1H), 8,61 (dd, J = 5,1, 1,8 Hz, 1H), 8,10 (d, J = 8,4 Hz, 2H), 7,78-7,71 (m, 1H), 7,36 10 (s, 1H), 7,29-7,22 (m, 1H), 7,08 (d, J = 8,4 Hz, 2H), 6,90 (s, 1H), 4,94-4,72 y 4,50-4,25 (cada m, cada 1H), 3,75-3,56 NMR: δ 8.83 (d, J = 2.4, 0.6 Hz, 1H), 8.61 (dd, J = 5.1, 1.8 Hz, 1H), 8.10 (d, J = 8.4 Hz, 2H), 7.78-7.71 (m, 1H), 7.36 10 (s, 1H), 7.29-7.22 (m, 1H), 7.08 (d , J = 8.4 Hz, 2H), 6.90 (s, 1H), 4.94-4.72 and 4.50-4.25 (every m, every 1H), 3.75-3.56

y 3,45-3,24 (cada m, cada 1H), 2,36 (s, 3H), 1,79-1,63 (m, 1H), 1,16-0,80 (m, 6H). and 3.45-3.24 (every m, every 1H), 2.36 (s, 3H), 1.79-1.63 (m, 1H), 1.16-0.80 (m, 6H) .

Ejemplo 2(82)Example 2 (82)

Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico 15 3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid 15

TLC: Fr 0,29 (cloroformo:metanol = 9:1); RMN: δ 8,87 (d, J = 1,8 Hz, 1H), 8,63 (dd, J = 5,1, 1,8 Hz, 1H), 8,13 (d, J = 1,8 Hz, 1H), 8,03 (dd, J = 8,1, 1,8 Hz, TLC: Fr 0.29 (chloroform: methanol = 9: 1); NMR: δ 8.87 (d, J = 1.8 Hz, 1H), 8.63 (dd, J = 5.1, 1.8 Hz, 1H), 8.13 (d, J = 1.8 Hz, 1H), 8.03 (dd, J = 8.1, 1.8 Hz,

20 1H), 7,73-7,66 (m, 1H), 7,40 (s, 1H), 7,36 (dd, J = 8,1, 5,1 Hz, 1H), 7,05 (d, J = 8,1 Hz, 1H), 6,96 (s, 1H), 4,92-4,74 y 4,54-4,34 (cada m, cada 1H), 3,72-3,63 y 3,50-3,33 (cada m, cada 1H), 2,39 (s, 3H), 1,84-1,68 (m, 1H), 1,20-0,92 (m, 6H). 1H), 7.73-7.66 (m, 1H), 7.40 (s, 1H), 7.36 (dd, J = 8.1, 5.1 Hz, 1H), 7.05 ( d, J = 8.1 Hz, 1H), 6.96 (s, 1H), 4.92-4.74 and 4.54-4.34 (every m, every 1H), 3.72-3, 63 and 3.50-3.33 (every m, every 1H), 2.39 (s, 3H), 1.84-1.68 (m, 1H), 1.20-0.92 (m, 6H ).

Ejemplo 2(84)25 Ácido 3-metoxi-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (84) 25 3-Methoxy-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,38 (cloroformo:metanol = 9:1); TLC: Fr 0.38 (chloroform: methanol = 9: 1);

30 RMN: δ 8,47 (d, J = 4,8 Hz, 1H), 7,75-7,60 (m, 3H), 7,56 (d, J = 1,5 Hz, 1H), 7,20-7,15 (m, 2H), 7,12 (s, 1H), 6,65 (s, 1H), 4,84 (a, 1H), 4,66 (a, 1H), 3,92 (s, 3H), 3,61 (a, 2H), 2,22 (s, 3H), 2,18 (s, 3H), 1,80-1,60 (m, 1H), 0,96 (a, 6H). NMR: δ 8.47 (d, J = 4.8 Hz, 1H), 7.75-7.60 (m, 3H), 7.56 (d, J = 1.5 Hz, 1H), 7 , 20-7.15 (m, 2H), 7.12 (s, 1H), 6.65 (s, 1H), 4.84 (a, 1H), 4.66 (a, 1H), 3, 92 (s, 3H), 3.61 (a, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 1.80-1.60 (m, 1H), 0.96 (a, 6H).

Ejemplo 2(85) Ácido 3-metoxi-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (85) 3-Methoxy-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

5 TLC: Fr 0,35 (cloroformo:metanol = 9:1); RMN: δ 8,86 (dd, J = 2,1, 0,9 Hz, 1H), 8,57 (dd, J = 5,1,1,5 Hz, 1H), 7,75-7,65 (m, 2H), 7,61 (d, J = 1,5 Hz, 1H), 7,307,20 (m, 2H), 6,92 (d, J = 7,8 Hz, 1H), 6,72 (s, 1H), 4,75 (d, J = 12,3 Hz, 1H), 4,43 (d, J = 12,3 Hz, 1H), 3,93 (s, 3H), 3,75-3,60 (m, 1H), 3,45-3,35 (m, 1H), 2,29 (s, 3H), 2,25 (s, 3H), 1,85-1,65 (m, 1H), 1,09 (d, J = 6,3 Hz, 3H), 0,92 (d, J 5 TLC: Fr 0.35 (chloroform: methanol = 9: 1); NMR: δ 8.86 (dd, J = 2.1, 0.9 Hz, 1H), 8.57 (dd, J = 5.1.1.5 Hz, 1H), 7.75-7.65 (m, 2H), 7.61 (d, J = 1.5 Hz, 1H), 7.307.20 (m, 2H), 6.92 (d, J = 7.8 Hz, 1H), 6.72 (s, 1H), 4.75 (d, J = 12.3 Hz, 1H), 4.43 (d, J = 12.3 Hz, 1H), 3.93 (s, 3H), 3.75 -3.60 (m, 1H), 3.45-3.35 (m, 1H), 2.29 (s, 3H), 2.25 (s, 3H), 1.85-1.65 (m , 1H), 1.09 (d, J = 6.3 Hz, 3H), 0.92 (d, J

10 = 6,3 Hz, 3H). 10 = 6.3 Hz, 3H).

Ejemplo 2(86) Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (86) 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,61 (cloroformo:metanol:agua = 8:2: 0,2); RMN (DMSO-d6): δ 12,87 (s a, I H), 8,64 (d, J = 1,8 Hz, 1H), 8,59 (dd, J = 4,8, 1,8 Hz, 1H), 7,91 (dt, J = 8,1, 1,8 Hz, 1H), 7,73 (s, 1H), 7,67 (d, J = 8,1 Hz, 1H), 7,35 (dd, J = 8,1, 4,8 Hz, 1H), 7,04-6,96 (m, 3H), 4,92 (a, 1H), 4,66 (a, TLC: Fr 0.61 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSO-d6): δ 12.87 (sa, IH), 8.64 (d, J = 1.8 Hz, 1H), 8.59 (dd, J = 4.8, 1.8 Hz, 1H), 7.91 (dt, J = 8.1, 1.8 Hz, 1H), 7.73 (s, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.35 (dd, J = 8.1, 4.8 Hz, 1H), 7, 04-6.96 (m, 3H), 4.92 (a, 1H), 4.66 (a,

20 1H), 3,48-3,22 (a, 2H), 2,23 (s, 3H), 2,22 (s, 3H), 2,15 (s, 3H), 1,49 (sep, J = 6,9 Hz, 1H), 0,98-0,75 (m, 6H). 1H), 3.48-3.22 (a, 2H), 2.23 (s, 3H), 2.22 (s, 3H), 2.15 (s, 3H), 1.49 (sep, J = 6.9 Hz, 1H), 0.98-0.75 (m, 6H).

Ejemplo 2(87) Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (87) 3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,66 (cloroformo:metanol:agua = 8:2: 0,2); RMN (DMSOd6): δ 12,88 (s, 1H), 8,47 (d, J = 4,5 Hz, 1H), 7,87 (dt, J = 1,5, 7,8 Hz, 1H), 7,75 (s, 1H), 7,71 (d, J = 7,8 Hz, 1H), 7,63 (d, J = 7,8 Hz, 1H), 7,42 (ddd, J = 7,8, 4,5, 1,5 Hz, 1H), 7,16 (d, J = 7,8 Hz, 1H), 6,93 (s, 1H), 6,91 (s, TLC: Fr 0.66 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSOd6): δ 12.88 (s, 1H), 8.47 (d, J = 4.5 Hz, 1H), 7.87 (dt, J = 1.5, 7.8 Hz, 1H) , 7.75 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.42 (ddd, J = 7.8, 4.5, 1.5 Hz, 1H), 7.16 (d , J = 7.8 Hz, 1H), 6.93 (s, 1H), 6.91 (s,

30 1H), 4,80 (a, 2H), 3,57 (d, J = 6,6 Hz, 2H), 2,25 (s, 3H), 2,18 (s, 3H), 2,09 (s, 3H), 1,49 (sept, J = 6,6 Hz, 1H), 0,81 (d, J = 6,6 Hz, 6H). 30 1H), 4.80 (a, 2H), 3.57 (d, J = 6.6 Hz, 2H), 2.25 (s, 3H), 2.18 (s, 3H), 2.09 (s, 3H), 1.49 (sept, J = 6.6 Hz, 1H), 0.81 (d, J = 6.6 Hz, 6H).

Ejemplo 2(88) Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico Example 2 (88) 3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid

5 TLC: Fr 0,31 (cloroformo:metanol = 9:1); RMN: δ 8,83 (d, J = 1,8 Hz, 1H), 8,61 (dd, J = 5,4, 1,8 Hz, 1H), 7,93 (d, J = 8,1 Hz, 1H), 7,92 (s, 1H), 7,78 (dt, J = 8,1, 1,8 Hz 1H), 7,34 (s, 1H), 7,23 (dd, J = 8,1, 5,4 Hz, 1H), 6,95 (d, J = 8,1 Hz, 1H), 6,94 (s, 1H), 4,88-4,65 y 4,54-4,34 (cada m, cada 1H), 3,71 -3,53 y 3,43-3,24 (cada m, cada 1H), 2,36 (s, 3H), 2,27 (s, 3H), 1,78-1,63 (m, 1H), 1,08-0,79 5 TLC: Fr 0.31 (chloroform: methanol = 9: 1); NMR: δ 8.83 (d, J = 1.8 Hz, 1H), 8.61 (dd, J = 5.4, 1.8 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.92 (s, 1H), 7.78 (dt, J = 8.1, 1.8 Hz 1H), 7.34 (s, 1H), 7.23 (dd, J = 8.1, 5.4 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.94 (s, 1H), 4.88-4.65 and 4.54-4 , 34 (every m, every 1H), 3.71 -3.53 and 3.43-3.24 (every m, every 1H), 2.36 (s, 3H), 2.27 (s, 3H) , 1.78-1.63 (m, 1H), 1.08-0.79

10 (m, 6H). 10 (m, 6H).

Ejemplo 2(89) Ácido 4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (89) 4- [2- [N-Isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,3 (cloroformo:metanol = 10:1); RMN: δ 8,46 (m, 1H), 8,09-8,05 (m, 2H), 7,71 -7,60 (m, 2H), 7,28-7,25 (m, 2H), 7,20 (m, 1H), 7,09 (s, 1H), 6,62 (s, 1H), 5,02-4,50 (m, 2H), 3,83-3,43 (m, 2H), 2,21 (s, 3H), 2,17 (s, 3H), 1,67 (m, 1H), 1,04-0,82 (m, 6H). TLC: Fr 0.3 (chloroform: methanol = 10: 1); NMR: δ 8.46 (m, 1H), 8.09-8.05 (m, 2H), 7.71-7.60 (m, 2H), 7.28-7.25 (m, 2H) , 7.20 (m, 1H), 7.09 (s, 1H), 6.62 (s, 1H), 5.02-4.50 (m, 2H), 3.83-3.43 (m, 2H), 2.21 (s, 3H), 2.17 (s, 3H), 1.67 (m, 1H), 1.04-0.82 (m, 6H).

Ejemplo 2(90) Ácido 4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico Example 2 (90) 4- [2- [N-Isopropyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid

25 TLC: Fr 0,44 (cloroformo:metanol = 9:1); RMN: δ 8,70-8,60 (m, 1H), 7,84 (d, J = 7,5 Hz, 1H), 7,79 (d, J = 15,9 Hz, 1H), 7,71 (dt, J = 1,8, 7,5 Hz, 1H), 7,55 (d, J = 8,4 Hz, 2H), 7,39 (d, J = 8,4 Hz, 2H), 7,35-7,25 (m, 1H), 6,99 (s, 1H), 6,96 (s, 1H), 6,48 (d, J = 15,9 Hz, 1H), 4,96 (d, J = 12,3 Hz, 1H), 4,92 (d, J = 12,3 Hz, 1H), 4,75-4,60(m, 1H), 2,26 (s, 3H), 1,14 (d, J = 6,9 Hz, 3H), 1,11 (d, J = 25 TLC: Fr 0.44 (chloroform: methanol = 9: 1); NMR: δ 8.70-8.60 (m, 1H), 7.84 (d, J = 7.5 Hz, 1H), 7.79 (d, J = 15.9 Hz, 1H), 7, 71 (dt, J = 1.8, 7.5 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.35-7.25 (m, 1H), 6.99 (s, 1H), 6.96 (s, 1H), 6.48 (d, J = 15.9 Hz, 1H), 4.96 (d, J = 12.3 Hz, 1H), 4.92 (d, J = 12.3 Hz, 1H), 4.75-4.60 (m, 1H), 2.26 (s, 3H) , 1.14 (d, J = 6.9 Hz, 3H), 1.11 (d, J =

30 6,9 Hz, 3H). 30 6.9 Hz, 3H).

Ejemplo 2(91) Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]4-metil-5-clorofenoxmetil]cinámico Example 2 (91) 3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] 4-methyl-5-chlorophenoxmethyl] cinnamic acid

TLC: Fr 0,37 (cloroformo:metanol = 9:1); RMN: δ 8,50-8,40 (m, 1H), 7,77 (d, J = 15,9 Hz, 1H), 7,75-7,60 (m, 2H), 7,40-7,35 (m, 2H), 7,25-7,20 (m, 2H), 7,15 (d, J = 8,4 Hz, 1H), 6,90 (s, 1H), 6,49 (d, J = 15,9 Hz, 1H), 4,73 (a, 2H), 3,60 (a, 2H), 2,29 (s, 3H), 2,28 (s, 3H), 1,701,55 (m, 1H), 0,91 (d, J = 6, 6 Hz, 6H). TLC: Fr 0.37 (chloroform: methanol = 9: 1); NMR: δ 8.50-8.40 (m, 1H), 7.77 (d, J = 15.9 Hz, 1H), 7.75-7.60 (m, 2H), 7.40-7 , 35 (m, 2H), 7.25-7.20 (m, 2H), 7.15 (d, J = 8.4 Hz, 1H), 6.90 (s, 1H), 6.49 (d, J = 15.9 Hz, 1H), 4.73 (a, 2H), 3.60 (a, 2H), 2.29 (s, 3H), 2.28 (s, 3H), 1,701.55 (m, 1H), 0.91 (d, J = 6, 6 Hz, 6H).

Ejemplo 2(92) Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (92) 3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,36 (diclorometano:metanol = 20:1); TLC: Fr 0.36 (dichloromethane: methanol = 20: 1);

EM (FAB, Pos.): 509 (M + H)+. MS (FAB, Pos.): 509 (M + H) +.

15 Ejemplo 2(93) Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (93) 4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

20 TLC: Fr 0,27 (cloroformo:metanol = 10:1); EM (APCI, Neg. 20V): 493 (M -H)-. TLC: Fr 0.27 (chloroform: methanol = 10: 1); MS (APCI, Neg. 20V): 493 (M-H) -.

Ejemplo 2(94)Example 2 (94)

Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico 25 3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,33 (diclorometano:metanol = 20:1); EM (FAB, Pos.): 509 (M + H)+. TLC: Fr 0.33 (dichloromethane: methanol = 20: 1); MS (FAB, Pos.): 509 (M + H) +.

Ejemplo 2(95) Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (95) 3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,43 (cloroformo:metanol = 3:1); TLC: Fr 0.43 (chloroform: methanol = 3: 1);

RMN: δ 8,88-8,82 (m, 1H), 8,61-8,52 (m, 1H), 7,75-7,68 (m, 1H), 7,61 (d, J = 15,9 Hz, 1H), 7,52 (d, J = 1,5 Hz, 1H), NMR: δ 8.88-8.82 (m, 1H), 8.61-8.52 (m, 1H), 7.75-7.68 (m, 1H), 7.61 (d, J = 15.9 Hz, 1H), 7.52 (d, J = 1.5 Hz, 1H),

7,47 (d, J = 8,1 Hz, 1H), 7,32-7,20 (m, 2H), 6,97 (d, J = 8,1 Hz, 1H), 6,70 (s, 1H), 6,50 (d, J = 15,9 Hz, 1H), 4,88-4,75 7.47 (d, J = 8.1 Hz, 1H), 7.32-7.20 (m, 2H), 6.97 (d, J = 8.1 Hz, 1H), 6.70 (s , 1H), 6.50 (d, J = 15.9 Hz, 1H), 4.88-4.75

5 y 4,53-4,41 (cada m, cada 1H), 3,74-3,58 y 3,48-3,32 (cada m, cada 1H), 2,29 y 2,25 (cada s, cada 3H), 1,82-1,63 5 and 4.53-4.41 (every m, every 1H), 3.74-3.58 and 3.48-3.32 (every m, every 1H), 2.29 and 2.25 (every s , every 3H), 1.82-1.63

(m, 1H), 1,15-0,82 (m, 6H). (m, 1H), 1.15-0.82 (m, 6H).

Ejemplo 2(96)Example 2 (96)

Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico 10 3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid 10

TLC: Fr 0,36 (cloroformo:metanol = 9:1); TLC: Fr 0.36 (chloroform: methanol = 9: 1);

RMN (DMSO-d6): δ 8,65 (m, 2H), 7,94 (m, 1H), 7,54 (d, J = 16,2 Hz) y 7,51 (s) total 2H, 7,43 (d, J = 8,1 Hz, 1H), 7,38 15 (dd, J = 8,1, 4,8 Hz, 1H), 7,26 (s, 1H), 7,22 (s, 1H), 6,98 (d, J = 8,1 Hz, 1H), 6,53 (d, J = 16,2 Hz, 1H), 5,00-4,85 (m, NMR (DMSO-d6): δ 8.65 (m, 2H), 7.94 (m, 1H), 7.54 (d, J = 16.2 Hz) and 7.51 (s) total 2H, 7 , 43 (d, J = 8.1 Hz, 1H), 7.38 15 (dd, J = 8.1, 4.8 Hz, 1H), 7.26 (s, 1H), 7.22 (s , 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.53 (d, J = 16.2 Hz, 1H), 5.00-4.85 (m,

2H), 3,48-3,10 (m, 2H, cubierto con H2O en DMSO-d6), 2,34 (s, 3H), 2,21 (s, 3H), 1,48 (m, 1H), 0,93 (m, 6H). 2H), 3.48-3.10 (m, 2H, covered with H2O in DMSO-d6), 2.34 (s, 3H), 2.21 (s, 3H), 1.48 (m, 1H) , 0.93 (m, 6H).

Ejemplo 2(98)Example 2 (98)

Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico 20 3-methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,45 (cloroformo:metanol = 9:1); TLC: Fr 0.45 (chloroform: methanol = 9: 1);

RMN (DMSO-d6): δ 7,79 (s, 1H), 7,75 (d, J = 8,0 Hz, 1H), 7,59 (d, J = 8,0 Hz, 1H), 7,11 (s, 1H), 6,90 (d, J = 3,3 Hz, 25 1H), 6,82 (s, 1H), 6,30-6,20 (m, 1H), 5,08 (s, 2H), 4,30-4,20 (m, 1H), 2,87 (t, J = 7,5 Hz, 2H), 2,79 (t, J = 7,5 Hz, 2H), NMR (DMSO-d6): δ 7.79 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7 , 11 (s, 1H), 6.90 (d, J = 3.3 Hz, 25 1H), 6.82 (s, 1H), 6.30-6.20 (m, 1H), 5.08 (s, 2H), 4.30-4.20 (m, 1H), 2.87 (t, J = 7.5 Hz, 2H), 2.79 (t, J = 7.5 Hz, 2H) ,

2,35 (s, 3H), 2,28 (s, 3H), 2,10-1,95 (m, 2H), 0,97 (d, J = 6,6 Hz, 6H). 2.35 (s, 3H), 2.28 (s, 3H), 2.10-1.95 (m, 2H), 0.97 (d, J = 6.6 Hz, 6H).

Ejemplo 2(99)Example 2 (99)

Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico 30 3-methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid 30

TLC: Fr 0,50 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,60-7,50 (m, 4H), 7,11 (s, 1H), 6,89 (d, J = 3,3 Hz, 1H), 6,80 (s, 1H), 6,52 (d, J = 16,2 Hz, 1H), 35 6,30-6,20 (m, 1H), 5,04 (d, J = 13,5 Hz, 1H), 5,01 (d, J = 13,5 Hz, 1H), 4,30-4,20 (m, 1H), 2,87 (t, J = 7,2 Hz, 2H), 2,78 (t, J = 7,2 Hz, 2H), 2,32 (s, 3H), 2,28 (s, 3H), 2,10-1,95 (m, 2H), 0,97 (d, J = 6,6 Hz, 6H). TLC: Fr 0.50 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.60-7.50 (m, 4H), 7.11 (s, 1H), 6.89 (d, J = 3.3 Hz, 1H), 6.80 (s, 1H), 6.52 (d, J = 16.2 Hz, 1H), 35 6.30-6.20 (m, 1H), 5.04 (d, J = 13.5 Hz, 1H), 5 , 01 (d, J = 13.5 Hz, 1H), 4.30-4.20 (m, 1H), 2.87 (t, J = 7.2 Hz, 2H), 2.78 (t, J = 7.2 Hz, 2H), 2.32 (s, 3H), 2.28 (s, 3H), 2.10-1.95 (m, 2H), 0.97 (d, J = 6 , 6 Hz, 6H).

Ejemplo 2(100) Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (100) 4- [6- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

5 TLC: Fr 0,42 (cloroformo:metanol = 9:1); RMN: δ 7,79 (d, J = 16,2 Hz, 1H), 7,57 (d, J = 8,4 Hz, 2H), 7,51 (d, J = 8,4 Hz, 2H), 6:89 (s, 1H), 6,84 (s, 1H), 6,80 (d, J = 3,3 Hz, 1H), 6,46 (d, J = 16,2 Hz, 1H), 6,02 (m, 1H), 5,14-5,00 (m, 2H), 4,46 (m, 1H), 2,91-2,80 (m, 4H), 2,31 (s, 3H), 2,14-2,02 (m, 2H), 1,11 (d, J = 6,6 Hz, 3H), 1,10 (d, J = 6,6 Hz, 3H). 5 TLC: Fr 0.42 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 16.2 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H) , 6:89 (s, 1H), 6.84 (s, 1H), 6.80 (d, J = 3.3 Hz, 1H), 6.46 (d, J = 16.2 Hz, 1H) , 6.02 (m, 1H), 5.14-5.00 (m, 2H), 4.46 (m, 1H), 2.91-2.80 (m, 4H), 2.31 (s , 3H), 2.14-2.02 (m, 2H), 1.11 (d, J = 6.6 Hz, 3H), 1.10 (d, J = 6.6 Hz, 3H).

10 Ejemplo 2(101)Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico Example 2 (101) 3-methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl acid ]benzoic

15 TLC: Fr 0,44 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,79 (s, 1H), 7,77 (d, J = 8,4 Hz, 1H), 7,57 (s, 1H), 7,28 (d, J = 8,4 Hz, 1H), 7,27 (s, 1H), 7,23 (s, 1H), 4,97 (m, 2H), 4,77 (m, 1H), 4,72 (m, 1H), 4,21 (m, 2H), 2,34 (s, 3H), 2,32 (s, 3H), 2,22 (s, 3H), 1,68 (s, 3H). TLC: Fr 0.44 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.79 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.57 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.27 (s, 1H), 7.23 (s, 1H), 4.97 (m, 2H), 4.77 (m, 1H), 4.72 (m, 1H), 4.21 (m, 2H), 2.34 (s, 3H), 2.32 (s, 3H), 2.22 (s, 3H), 1.68 (s, 3H).

20 Ejemplo 2(103) Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (103) 3-methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

25 TLC: Fr 0,24 (diclorometano:metanol = 19:1); RMN (DMSOd6): δ 7,77-7,73 (m, 2H), 7,50 (s a, 1H), 7,23 (d, J = 6,9 Hz, 1H), 6,99 (s, 1H), 6,96 (s, 1H), 4,87 (s a, 2H), 4,74 (s a, 1H), 4,71 (s a, 1H), 4,20 (s a, 2H), 2,28 (s, 3H), 2,19 (s, 3H), 2,16 (d, J = 0,6 Hz, 3H), 2,11 (s, 3H), 1,68 (s, 3H). 25 TLC: Rf 0.24 (dichloromethane: methanol = 19: 1); NMR (DMSOd6): δ 7.77-7.73 (m, 2H), 7.50 (sa, 1H), 7.23 (d, J = 6.9 Hz, 1H), 6.99 (s, 1H), 6.96 (s, 1H), 4.87 (sa, 2H), 4.74 (sa, 1H), 4.71 (sa, 1H), 4.20 (sa, 2H), 2, 28 (s, 3H), 2.19 (s, 3H), 2.16 (d, J = 0.6 Hz, 3H), 2.11 (s, 3H), 1.68 (s, 3H).

30 Ejemplo 2(104) Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (104) 3-methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

35 TLC: Fr 0,43 (cloroformo:metanol = 9:1); RMN: δ 7,96(d, J = 8,1 Hz, 1H), 7,93 (s, 1H), 7,89 (d, J = 3,0 Hz, 1H), 7,58 (d, J = 8,1 Hz, 1H), 7,46 (d, J = 3,0 Hz, TLC: Fr 0.43 (chloroform: methanol = 9: 1); NMR: δ 7.96 (d, J = 8.1 Hz, 1H), 7.93 (s, 1H), 7.89 (d, J = 3.0 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 3.0 Hz,

1H), 6,95 (s, 1H), 6,86 (s, 1H), 5,05 y 4,99 (cada d, J = 13,5 Hz, cada 1H), 4,69 (sept, J = 6,6 Hz, 1H), 2,94-2,79 (m, 4H), 2,39 (s, 3H), 2,16-2,02 (m, 2H), 1,18 y 1,15 (cada d, J = 6,6 Hz, cada 3H). 1H), 6.95 (s, 1H), 6.86 (s, 1H), 5.05 and 4.99 (every d, J = 13.5 Hz, every 1H), 4.69 (sept, J = 6.6 Hz, 1H), 2.94-2.79 (m, 4H), 2.39 (s, 3H), 2.16-2.02 (m, 2H), 1.18 and 1, 15 (every d, J = 6.6 Hz, every 3H).

Ejemplo 2(105) Ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (105) 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,41 (cloroformo:metanol = 9:1), TLC: Fr 0.41 (chloroform: methanol = 9: 1),

10 RMN: δ 7,93 (d, J = 8,4 Hz, 1H), 7,92 (s, 1H), 7,71 (d, J = 3,0 Hz, 1H), 7,35 (d, J = 3,0 Hz, 1H), 7,31 (d, J = 8,4 Hz, 1H), 7,15 (s, 1H), 6,77 (s, 1H), 5,02-4,64 (m, 2H), 3,81-3,43 (m, 2H), 2,95-2,76 (m, 4H), 2,34 (s, 3H), 2,17-2,01 (m, 2H), 1,82-1,64 (m, 1H), 1,08-0,83 (m, 6H). 10 NMR: δ 7.93 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H), 7.71 (d, J = 3.0 Hz, 1H), 7.35 (d , J = 3.0 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.15 (s, 1H), 6.77 (s, 1H), 5.02-4 , 64 (m, 2H), 3.81-3.43 (m, 2H), 2.95-2.76 (m, 4H), 2.34 (s, 3H), 2.17-2.01 (m, 2H), 1.82-1.64 (m, 1H), 1.08-0.83 (m, 6H).

Ejemplo 2(106)15 Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (106) 15-Methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,34 (diclorometano:metanol = 19:1); TLC: Fr 0.34 (dichloromethane: methanol = 19: 1);

20 RMN: δ 7,97 (d, J = 8,1 Hz, 1H), 7,94 (s, 1H), 7,57 (d, J = 8,1 Hz, 1H), 7,00 (s a, 1H), 6,94 (s, 1H), 6,86 (s, 1H), 5,05 (d, J = 13,5 Hz, 1H), 4,99 (d, J = 13,5 Hz, 1H), 4,70 (m, 1H), 2,92-2,81 (m, 4H), 2,47 (s, 3H), 2,39 (s, 3H), 2,09 (m, 2H), 1,18 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). NMR: δ 7.97 (d, J = 8.1 Hz, 1H), 7.94 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.00 (sa , 1H), 6.94 (s, 1H), 6.86 (s, 1H), 5.05 (d, J = 13.5 Hz, 1H), 4.99 (d, J = 13.5 Hz , 1H), 4.70 (m, 1H), 2.92-2.81 (m, 4H), 2.47 (s, 3H), 2.39 (s, 3H), 2.09 (m, 2H), 1.18 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H).

Ejemplo 2(107)25 Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (107) 25 4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,37 (cloroformo:metanol = 10:1); TLC: Fr 0.37 (chloroform: methanol = 10: 1);

30 RMN: δ 8,13 (d, J = 8,1 Hz, 2H), 7,88 (d, J = 3,3 Hz, 1H), 7,51 (d, J = 8,1 Hz, 2H), 7,44 (d, J = 3,3 Hz, 1H), 6,95 (s, 1H), 6,84 (s, 1H), 5,06 (d, J = 13,5 Hz, 1H), 5,05 (d, J = 13,5 Hz, 1H), 4,71 (m, 1H), 2,92-2,78 (m, 4H), 2,14-2,02 (m, 2H), 1,18 (d, J = 6,6 Hz, 3H), 1,16(d, J = 6,6 Hz, 3H). NMR: δ 8.13 (d, J = 8.1 Hz, 2H), 7.88 (d, J = 3.3 Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H ), 7.44 (d, J = 3.3 Hz, 1H), 6.95 (s, 1H), 6.84 (s, 1H), 5.06 (d, J = 13.5 Hz, 1H ), 5.05 (d, J = 13.5 Hz, 1H), 4.71 (m, 1H), 2.92-2.78 (m, 4H), 2.14-2.02 (m, 2H), 1.18 (d, J = 6.6 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H).

Ejemplo 2(108) Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (108) 4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

5 TLC: Fr 0,35 (cloroformo:metanol = 10:1); RMN: δ 8,11 (d, J = 8,1 Hz, 2H), 7,71 (d, J = 3,3 Hz, 1H), 7,35 (d, J = 3,3 Hz, 1H), 7,34 (d, J = 8,1 Hz, 2H), 7,15 (s, 1H), 6,75 (s, 1H), 4,97 (m, 1H), 4,77 (m, 1H), 3,80-3,47 (m,2H), 2,89-2,82 (m, 4H), 2,15-2,01 (m, 2H), 1,73 (m, 1H), 1,05-0,85 (m, 6H). 5 TLC: Fr 0.35 (chloroform: methanol = 10: 1); NMR: δ 8.11 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 3.3 Hz, 1H), 7.35 (d, J = 3.3 Hz, 1H) , 7.34 (d, J = 8.1 Hz, 2H), 7.15 (s, 1H), 6.75 (s, 1H), 4.97 (m, 1H), 4.77 (m, 1H), 3.80-3.47 (m, 2H), 2.89-2.82 (m, 4H), 2.15-2.01 (m, 2H), 1.73 (m, 1H) , 1.05-0.85 (m, 6H).

10 Ejemplo 2(109)Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 2 (109) 4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

15 TLC : Fr 0,41 (cloroformo:metanol =9:1); RMN: δ 8,11 (d, J = 8,4 Hz, 2H), 7,50 (d, J = 8,4 Hz, 2H), 6,98 (d, J = 0,9 Hz, 1H), 6,94 (s, 1H), 6,84 (s, 1H), 5,115,00 (m, 2H), 4,71 (m, 1H), 2,91-2,79 (m, 4H), 2,47 (d, J = 0,9 Hz, 3H), 2,15-2,03 (m, 2H), 1,18 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR: δ 8.11 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 0.9 Hz, 1H) , 6.94 (s, 1H), 6.84 (s, 1H), 5,115.00 (m, 2H), 4.71 (m, 1H), 2.91-2.79 (m, 4H), 2.47 (d, J = 0.9 Hz, 3H), 2.15-2.03 (m, 2H), 1.18 (d, J = 6.6 Hz, 3H), 1.15 (d , J = 6.6 Hz, 3H).

20 Ejemplo 2(110)Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (110) 4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

25 TLC: Fr 0,40 (cloroformo:metanol = 9:1); RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,56 (d, J = 8,4 Hz, 2H), 7,45 (d, J = 8,4 Hz, 2H), 6,98 (d, J = 0,6 Hz, 1H), 6,92 (s, 1H), 6,85 (s, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,06-4,95 (m, 2H), 4,70 (m, 1H), 2,92-2,78 (m, 4H), 2,46 (d, J = 0,6 Hz, 3H), 2,16-2,01 (m, 2H), 1,17 (d, J = 6,6 Hz, 3H), 1,14 (d, J = 6,6 Hz, 3H). 25 TLC: Fr 0.40 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H) , 6.98 (d, J = 0.6 Hz, 1H), 6.92 (s, 1H), 6.85 (s, 1H), 6.47 (d, J = 15.9 Hz, 1H) , 5.06-4.95 (m, 2H), 4.70 (m, 1H), 2.92-2.78 (m, 4H), 2.46 (d, J = 0.6 Hz, 3H ), 2.16-2.01 (m, 2H), 1.17 (d, J = 6.6 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H).

30 Ejemplo 2(111)Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (111) 3-methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,30 (diclorometano:metanol =19:1); RMN (DMSO-d6): δ 12,38 (s a, 1H), 7,57 (s a, 1H), 7,56 (d, J = 15,9 Hz, 1H), 7,53 (s, 1H), 7,49 (d a, J = 8,1 Hz, 1H), TLC: Fr 0.30 (dichloromethane: methanol = 19: 1); NMR (DMSO-d6): δ 12.38 (sa, 1H), 7.57 (sa, 1H), 7.56 (d, J = 15.9 Hz, 1H), 7.53 (s, 1H) , 7.49 (da, J = 8.1 Hz, 1H),

7,39 (d, J = 8,1 Hz, 1H), 7,13 (s, 1H), 6,83 (s, 1H), 6,53 (d, J = 15,9 Hz, 1H), 4,99 (s a, 2H), 4,47 (m, 1H), 2,87 (m, 2H), 2,77 (m, 2H), 2,37 (d, J = 0,9 Hz, 3H), 2,30 (s, 3H), 2,02 (m, 2H), 1,04 (d, J = 6,6 Hz, 3H), 1,00 (d, J = 6,6 Hz, 3H). 7.39 (d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 6.83 (s, 1H), 6.53 (d, J = 15.9 Hz, 1H), 4.99 (sa, 2H), 4.47 (m, 1H), 2.87 (m, 2H), 2.77 (m, 2H), 2.37 (d, J = 0.9 Hz, 3H ), 2.30 (s, 3H), 2.02 (m, 2H), 1.04 (d, J = 6.6 Hz, 3H), 1.00 (d, J = 6.6 Hz, 3H ).

Ejemplo 2(112) Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (112) 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

10 TLC: Fr 0,57 (cloroformo:metanol = 9:1); RMN: δ 8,10 (d, J = 8,1 Hz, 2H), 7,86 (d, J = 3,0 Hz, 1H), 7,49 (d, J = 8,1 Hz, 2H), 7,43 (d, J = 3,0 Hz, 1H), 6,85 (s, 1H), 6,75 (s, 1H), 5,04 (s, 2H), 4,72 (sept, J = 6,9 Hz, 1H). 2,23 (s, 3H), 2,15 (s, 3H), 1,19 (d, J = 6,9 Hz, 3H), 1,15 (d, J = 6,9 Hz, 3H). 10 TLC: Fr 0.57 (chloroform: methanol = 9: 1); NMR: δ 8.10 (d, J = 8.1 Hz, 2H), 7.86 (d, J = 3.0 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H) , 7.43 (d, J = 3.0 Hz, 1H), 6.85 (s, 1H), 6.75 (s, 1H), 5.04 (s, 2H), 4.72 (Sept, J = 6.9 Hz, 1H). 2.23 (s, 3H), 2.15 (s, 3H), 1.19 (d, J = 6.9 Hz, 3H), 1.15 (d, J = 6.9 Hz, 3H).

15 Ejemplo 2(113) Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (113) 4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

20 TLC: Fr 0,56 (cloroformo:metanol =9:1), RMN: δ 8,11 (d, J = 8,4 Hz, 2H), 7,70 (d, J = 3,0 Hz, 1H), 7,36-7,32 (m, 3H), 7,07 (s, 1H), 6,66 (s, 1H), 5,10-4,65 (m, 2H), 3,80-3,45 (m, 2H), 2,22 (s, 3H), 2,18 (s, 3H), 1,71 (sept, J = 6,9 Hz, 1H), 1,15-0,95 (m, 6H). 20 TLC: Fr 0.56 (chloroform: methanol = 9: 1), NMR: δ 8.11 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 3.0 Hz, 1H ), 7.36-7.32 (m, 3H), 7.07 (s, 1H), 6.66 (s, 1H), 5.10-4.65 (m, 2H), 3.80- 3.45 (m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 1.71 (sept, J = 6.9 Hz, 1H), 1.15-0.95 (m, 6H).

Ejemplo 3(114)25 Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 3 (114) 25 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

TLC: Fr 0,56 (cloroformo:metanol = 9:1); TLC: Fr 0.56 (chloroform: methanol = 9: 1);

30 RMN: δ 7,86 (d, J = 3,0 Hz, 1H), 7,79 (d, J = 15,9 Hz, 1H), 7,56 (d, J = 8,4 Hz, 2H), 7,42 (d, J = 8,4 Hz, 2H), 7,42 (d, J = 3,0 Hz, 1H), 6,84 (s, 1H), 6,76 (s, 1H), 6,46 (d, J = 15,9 Hz, 1H), 5,04(d, J = 11,7 Hz, 1 H),4,98(d, J = 11,7 Hz, 1H), 4,71 (sept, J = 6,6 Hz, 1H), 2:23 (s, 3H), 2,13 (s, 3H), 1,18 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). NMR: δ 7.86 (d, J = 3.0 Hz, 1H), 7.79 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H ), 7.42 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 3.0 Hz, 1H), 6.84 (s, 1H), 6.76 (s, 1H ), 6.46 (d, J = 15.9 Hz, 1H), 5.04 (d, J = 11.7 Hz, 1 H), 4.98 (d, J = 11.7 Hz, 1H) , 4.71 (sept, J = 6.6 Hz, 1H), 2:23 (s, 3H), 2.13 (s, 3H), 1.18 (d, J = 6.6 Hz, 3H) , 1.15 (d, J = 6.6 Hz, 3H).

Ejemplo 2(115) Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (115) 4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

5 TLC: Fr 0,58 (cloroformo:metanol = 9:1); RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,67 (d, J = 3,0 Hz, 1H), 7,55 (d, J = 8,4 Hz, 2H), 7,34 (d, J = 3,0 Hz, 1H), 7,27 (d, J = 8,4 Hz, 2H), 7,05 (s, 1H), 6,67 (s, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,00-4,62 (m, 2H), 3,80-3,45 (m, 2H), 2,22 (s, 3H), 2,17 (s, 3H), 1,70 (sept, J = 6,6 Hz, 1H), 1,10-0,96 (m, 6H). 5 TLC: Fr 0.58 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.67 (d, J = 3.0 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H) , 7.34 (d, J = 3.0 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.05 (s, 1H), 6.67 (s, 1H) , 6.47 (d, J = 15.9 Hz, 1H), 5.00-4.62 (m, 2H), 3.80-3.45 (m, 2H), 2.22 (s, 3H ), 2.17 (s, 3H), 1.70 (sept, J = 6.6 Hz, 1H), 1.10-0.96 (m, 6H).

10 Ejemplo 2(116)Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (116) 4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

15 TLC: Fr 0,39 (cloroformo:metanol = 10:1); RMN: δ 7,87 (d, J = 3,3 Hz, 1H), 7,80 (d, J = 15,9 Hz, 1H), 7,56 (d, J = 7,8 Hz, 2H), 7,45 (d, J = 7,8 Hz, 2H), 7,44 (d, J = 3,3 Hz, 1H), 6,94 (s, 1H), 6,85 (s, 1H), 6,48 (d, J = 15,9 Hz, 1H), 5,01 (d, J = 13,2 Hz, 1H), 5,00 (d, J = 13,2 Hz, 1H), 4,70 (m, 1H), 2,91-2,79 (m, 4H), 2,14-2,01 (m, 2H), 1,17 (d, J = 6,6 Hz, 3H), 1,15 (d, J = 6,6 Hz, 3H). TLC: Fr 0.39 (chloroform: methanol = 10: 1); NMR: δ 7.87 (d, J = 3.3 Hz, 1H), 7.80 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 7.8 Hz, 2H) , 7.45 (d, J = 7.8 Hz, 2H), 7.44 (d, J = 3.3 Hz, 1H), 6.94 (s, 1H), 6.85 (s, 1H) , 6.48 (d, J = 15.9 Hz, 1H), 5.01 (d, J = 13.2 Hz, 1H), 5.00 (d, J = 13.2 Hz, 1H), 4 , 70 (m, 1H), 2.91-2.79 (m, 4H), 2.14-2.01 (m, 2H), 1.17 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H).

20 Ejemplo 2(117)Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (117) 4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

25 TLC: Fr 0,40 (cloroformo:metanol = 10:1); RMN: δ 7,80 (d, J = 15,9 Hz, 1H), 7,69 (d, J = 3,3 Hz, 1H), 7,55 (d, J = 8,4 Hz, 2H), 7,34 (d, J = 3,3 Hz, 1H), 7,27 (d, J = 8,4 Hz, 2H), 7,14 (s, 1H), 6,75 (s, 1H), 6,48 (d, J = 15,9 Hz, 1H), 4,92 (m, 1H), 4,70 (m, 1H), 3,78-3,46 (m, 2H), 2,90-2,80 (m, 4H), 2,14-2,01 (m, 2H), 1,72 (m, 1H), 1,02-0,83 (m, 6H). 25 TLC: Fr 0.40 (chloroform: methanol = 10: 1); NMR: δ 7.80 (d, J = 15.9 Hz, 1H), 7.69 (d, J = 3.3 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H) , 7.34 (d, J = 3.3 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.14 (s, 1H), 6.75 (s, 1H) , 6.48 (d, J = 15.9 Hz, 1H), 4.92 (m, 1H), 4.70 (m, 1H), 3.78-3.46 (m, 2H), 2, 90-2.80 (m, 4H), 2.14-2.01 (m, 2H), 1.72 (m, 1H), 1.02-0.83 (m, 6H).

30 Ejemplo 2(118)Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (118) 3-methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,27 (cloroformo:metanol = 9:1); RMN: δ 8,00-7,90 (m, 2H), 7,87 (d, J = 3,0 Hz, 1H), 7,55 (d, J = 7,8 Hz, 1H), 7,44 (d, J = 3,0 Hz, 1H), 6,85 y 6,77 (cada s, cada 1H), 5,09-4,92 (m, 2H), 4,78-4,62 (m, 1H), 2,39 (s, 3H), 2,25 (s, 3H), 2,16 (s, 3H), 1,19 y 1,15 (cada d, J = 6,6 Hz, cada 3H). TLC: Fr 0.27 (chloroform: methanol = 9: 1); NMR: δ 8.00-7.90 (m, 2H), 7.87 (d, J = 3.0 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7, 44 (d, J = 3.0 Hz, 1H), 6.85 and 6.77 (every s, every 1H), 5.09-4.92 (m, 2H), 4.78-4.62 ( m, 1H), 2.39 (s, 3H), 2.25 (s, 3H), 2.16 (s, 3H), 1.19 and 1.15 (each d, J = 6.6 Hz, every 3H).

Ejemplo 2(119) Ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 2 (119) 3-methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

10 TLC: Fr 0,27 (cloroformo:metanol = 9:1); RMN: δ 7,95-7,89 (m, 2H), 7,70 y 7,34 (cada d, J = 3,3 Hz, cada 1H), 7,32-7,29 (m, 1H), 7,06 y 6,69 (cada s, cada 1H), 5,00-4,68 (m, 2H), 3,78-3,48 (m, 2H), 2,34 (s, 3H), 2,23 (s, 3H), 2,18 (s, 3H), 1,80-1,65 (m, 1H), 1,08-0,82 (m, 6H). 10 TLC: Fr 0.27 (chloroform: methanol = 9: 1); NMR: δ 7.95-7.89 (m, 2H), 7.70 and 7.34 (every d, J = 3.3 Hz, every 1H), 7.32-7.29 (m, 1H) , 7.06 and 6.69 (every s, every 1H), 5.00-4.68 (m, 2H), 3.78-3.48 (m, 2H), 2.34 (s, 3H) , 2.23 (s, 3H), 2.18 (s, 3H), 1.80-1.65 (m, 1H), 1.08-0.82 (m, 6H).

15 Ejemplo 2(120) Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximatil]cinámico Example 2 (120) 3-methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoximatyl] cinnamic acid

20 TLC: Fr 0,25 (cloroformo:metanol = 9:1); RMN: δ 7,87 (d, J = 3,0 Hz, 1H), 7,77 (d, J = 16,2 Hz, 1H), 7,52-7,32 (m, 4H), 6,83 y 6,79 (cada s, cada 1H), 6,46 (d, J = 16,2 Hz, 1H), 5,05-4,87 (m, 2H), 4,75-4,62 (m, 1H), 2,36 (s, 3H), 2,25 (s, 3H),2,15 (s, 3H), 1,17 y 1,13 (cada d, J = 6,6 Hz, cada 3H). TLC: Fr 0.25 (chloroform: methanol = 9: 1); NMR: δ 7.87 (d, J = 3.0 Hz, 1H), 7.77 (d, J = 16.2 Hz, 1H), 7.52-7.32 (m, 4H), 6, 83 and 6.79 (every s, every 1H), 6.46 (d, J = 16.2 Hz, 1H), 5.05-4.87 (m, 2H), 4.75-4.62 ( m, 1H), 2.36 (s, 3H), 2.25 (s, 3H), 2.15 (s, 3H), 1.17 and 1.13 (each d, J = 6.6 Hz, every 3H).

25 Ejemplo 2(121) Ácido 3-metil-4-(2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico Example 2 (121) 3-methyl-4- (2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid

30 TLC: Fr 0,25 (cloroformo:metanol = 9:1); RMN: δ 7,76 (d, J = 16,2 Hz, 1H), 7,69 (d, J = 3,0 Hz, 1H), 7,42-7,3 (m, 2H), 7,34 (d, J = 3,0 Hz, 1H), 7,25-7,19 (m, 1H), 7,05 y 6,70 (cada s, cada 1H), 6,47 (d, J = 16,2 Hz, 1H), 4,95-4,62 (m, 2H), 3,75-3,48 (m, 2H), 2,31 (s, 3H), 2,24 (s, 3H), 2,18 (s, 3H), 1,78-1,62 (m, 1H), 1,78-1,62 (m, 6H). TLC: Fr 0.25 (chloroform: methanol = 9: 1); NMR: δ 7.76 (d, J = 16.2 Hz, 1H), 7.69 (d, J = 3.0 Hz, 1H), 7.42-7.3 (m, 2H), 7, 34 (d, J = 3.0 Hz, 1H), 7.25-7.19 (m, 1H), 7.05 and 6.70 (each s, every 1H), 6.47 (d, J = 16.2 Hz, 1H), 4.95-4.62 (m, 2H), 3.75-3.48 (m, 2H), 2.31 (s, 3H), 2.24 (s, 3H ), 2.18 (s, 3H), 1.78-1.62 (m, 1H), 1.78-1.62 (m, 6H).

Ejemplo 2(122) Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (122) 3-Methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

5 TLC: Fr 0,44 (cloroformo:metanol = 9:1); RMN: δ 7,88 (d, J = 3,0 Hz, 1H), 7,77 (d, J = 16,2 Hz, 1H), 7,51 (d, J = 8,1 Hz, 1H), 7,45 (d, J = 3,0 Hz, 1H), 7,42 (d, J = 8,1 Hz, 1H), 7,38 (s, 1H), 6,93 (s, 1H), 6,87 (s, 1H), 6,46 (d, J = 16,2 Hz, 1H), 5,02 y 4,95 (cada d, J = 12,9 Hz, cada 1H), 4,68 (sept, J = 6,6 Hz, 1H), 2,94-2,78 (m, 4H), 2,36 (s, 3H), 2,16-2,02 (m, 2H), 1,17 y 1,14 (cada d, J = 6,6 5 TLC: Fr 0.44 (chloroform: methanol = 9: 1); NMR: δ 7.88 (d, J = 3.0 Hz, 1H), 7.77 (d, J = 16.2 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H) , 7.45 (d, J = 3.0 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.38 (s, 1H), 6.93 (s, 1H) , 6.87 (s, 1H), 6.46 (d, J = 16.2 Hz, 1H), 5.02 and 4.95 (every d, J = 12.9 Hz, every 1H), 4, 68 (Sept, J = 6.6 Hz, 1H), 2.94-2.78 (m, 4H), 2.36 (s, 3H), 2.16-2.02 (m, 2H), 1 , 17 and 1.14 (each d, J = 6.6

10 Hz, cada 3H). 10 Hz, every 3H).

Ejemplo 2(123) Ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 2 (123) 3-Methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,39 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,98 (d, J = 3,0 Hz, 1H), 7,87 (d, J = 3,0 Hz, 1H), 7,56 (d, J = 16,2 Hz, 1H), 7,52 (s, 1H), 7,50 (d, J = 8,1 Hz, 1H), 7,18 (d, J = 8,1 Hz, 1H), 7,06 (s, 1H), 7,00 (s, 1H), 6,54 (d, J = 16,2 Hz, 1H), 5,04-4,66 (m, 2H), 3,57TLC: Fr 0.39 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.98 (d, J = 3.0 Hz, 1H), 7.87 (d, J = 3.0 Hz, 1H), 7.56 (d, J = 16, 2 Hz, 1H), 7.52 (s, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 7.00 (s, 1H), 6.54 (d, J = 16.2 Hz, 1H), 5.04-4.66 (m, 2H), 3.57

20 3,37 (m, 2H), 2,93-2,68 (m, 4H), 2,27 (s, 3H), 2,11-1,93 (m, 2H), 1,64-1,46 (m, 1H), 0,94-0,74 (m, 6H). 20 3.37 (m, 2H), 2.93-2.68 (m, 4H), 2.27 (s, 3H), 2.11-1.93 (m, 2H), 1.64-1 , 46 (m, 1H), 0.94-0.74 (m, 6H).

Ejemplo 2(124) Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-2-naftiloximetil]benzoico Example 2 (124) 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -2-naphthyloxymethyl] benzoic acid

TLC: Fr 0,33 (cloroformo:metanol = 9:1); RMN (CD3OD): δ 8,05 (d, J = 8,4 Hz, 2H), 7,82-7,75 (m, 3H), 7,53 (d, J = 8,4 Hz, 2H), 7,51-7,35 (m, 3H), 6,71 (d, J = 3,3 Hz, 1H), 6,05 (m, 1H), 5,42-4,95 (a, 2H), 3,62 (d, J = 7,5 Hz, 2H), 2,13 (s, 3H), 1,79-1,61 (m, 1H), 0,94 (d, J = 6,3 TLC: Fr 0.33 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 8.05 (d, J = 8.4 Hz, 2H), 7.82-7.75 (m, 3H), 7.53 (d, J = 8.4 Hz, 2H) , 7.51-7.35 (m, 3H), 6.71 (d, J = 3.3 Hz, 1H), 6.05 (m, 1H), 5.42-4.95 (a, 2H), 3.62 (d, J = 7.5 Hz, 2H), 2.13 ( s, 3H), 1.79-1.61 (m, 1H), 0.94 (d, J = 6.3

30 Hz, 6H). 30 Hz, 6H).

Ejemplo de Referencia 4 N-[4,5-dimetil-2-(2-metil-4-cianofenilmetiloxi)fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Reference Example 4 N- [4,5-dimethyl-2- (2-methyl-4-cyanophenylmethyloxy) phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

5 En una atmósfera de argón, una solución de ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5dimetilfenoximetil]benzoico preparada en el Ejemplo 2 (178 mg) en diclorometano (1,5 ml) se enfrió a 0 ºC, después se añadieron cloruro de oxalilo (48 μl) y una cantidad catalítica de N,N-dimetilformamida a la misma. Después, la solución se agitó durante 1 hora a temperatura ambiente, la mezcla de reacción se concentró a presión reducida y se In an argon atmosphere, a solution of 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid prepared in Example 2 ( 178 mg) in dichloromethane (1.5 ml) was cooled to 0 ° C, then oxalyl chloride (48 μl) and a catalytic amount of N, N-dimethylformamide were added thereto. Then, the solution was stirred for 1 hour at room temperature, the reaction mixture was concentrated under reduced pressure and was

10 destiló azeotrópicamente con tolueno. En una atmósfera de argón, el residuo se disolvió en diclorometano (1,5 ml) y se enfrió a 0 ºC. La solución se añadió mediante amoniaco acuoso al 28% (1 ml) y se agitó durante 5 minutos. La solución se añadió mediante agua y acetato de etilo. La fase orgánica se lavó, se secó y se concentró a presión reducida. En una atmósfera de argón, el residuo se disolvió en diclorometano (1,5 ml) y se enfrió a 0 ºC. La solución se añadió mediante piridina (0,18 ml) y ácido trifluorometanosulfónico anhídrido (0,12 ml) y se agitó durante 50 10 azeotropically distilled with toluene. Under an argon atmosphere, the residue was dissolved in dichloromethane (1.5 ml) and cooled to 0 ° C. The solution was added by 28% aqueous ammonia (1 ml) and stirred for 5 minutes. The solution was added by water and ethyl acetate. The organic phase was washed, dried and concentrated under reduced pressure. Under an argon atmosphere, the residue was dissolved in dichloromethane (1.5 ml) and cooled to 0 ° C. The solution was added by pyridine (0.18 ml) and trifluoromethanesulfonic acid anhydride (0.12 ml) and stirred for 50

15 minutos. La mezcla de reacción se vertió en agua, después se añadió mediante acetato de etilo. La fase orgánica se lavó, se secó y se concentró a presión reducida. El residuo se purificó por cromatografía en columna sobre gel de sílice (hexano -acetato de etilo), dando el compuesto del título (149 mg) que tenía los siguientes datos físicos. TLC: Fr 0,74 (n-hexano:acetato de etilo = 1:1). 15 minutes. The reaction mixture was poured into water, then added by ethyl acetate. The organic phase was washed, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the title compound (149 mg) which had the following physical data. TLC: Fr 0.74 (n-hexane: ethyl acetate = 1: 1).

20 Ejemplo 3 N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 3 N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

25 A N-[4,5-dimetil-2-(2-metil-4-cianofenilmetiloxi)fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida preparada en el Ejemplo de Referencia 4 (79 mg), se le añadió trimetilestaño azida (43 mg) y la mezcla se calentó a reflujo durante 7 horas y después se agitó durante 1 día a temperatura ambiente. La mezcla de reacción se añadió mediante metanol (3 ml) y ácido clorhídrico 2 N (2 ml) y después se agitó durante 2 horas. La solución se añadió mediante agua y acetato de etilo. La fase orgánica se lavó, se secó y se concentró a presión reducida. El residuo se lavó mediante hexano A- N- [4,5-dimethyl-2- (2-methyl-4-cyanophenylmethyloxy) phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide prepared in Reference Example 4 (79 mg) , trimethyltin azide (43 mg) was added and the mixture was heated at reflux for 7 hours and then stirred for 1 day at room temperature. The reaction mixture was added by methanol (3 ml) and 2 N hydrochloric acid (2 ml) and then stirred for 2 hours. The solution was added by water and ethyl acetate. The organic phase was washed, dried and concentrated under reduced pressure. The residue was washed with hexane.

30 acetato de etilo para dar el compuesto del título (81 mg) que tenía los siguientes datos físicos. TLC: Fr 0,52 (cloroformo:metanol:agua = 8:2: 0,2); EM (FAB, Pos.): 510 (M + H)+. 30 ethyl acetate to give the title compound (81 mg) that had the following physical data. TLC: Fr 0.52 (chloroform: methanol: water = 8: 2: 0.2); MS (FAB, Pos.): 510 (M + H) +.

Mediante los mismos procedimientos que se han descrito en los Ejemplos de Referencia 1 a 3 y el Ejemplo 3, se 35 obtuvieron los compuestos del título que tenían los siguientes datos físicos. By the same procedures as described in Reference Examples 1 to 3 and Example 3, the title compounds having the following physical data were obtained.

Ejemplo 3(1) N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 3 (1) N- [4-chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

5 TLC: Fr 0,40 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 530 (M)+. 5 TLC: Fr 0.40 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 530 (M) +.

Ejemplo 3(2) 10 N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida Example 3 (2) 10 N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide

TLC: Fr 0,52 (cloroformo:metanol:agua = 8:2: 0,2); 15 EM (FAB, Pos.): 496 (M + H)+. TLC: Fr 0.52 (chloroform: methanol: water = 8: 2: 0.2); 15 MS (FAB, Pos.): 496 (M + H) +.

Ejemplo 3(3) N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 3 (3) N- [4-chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

TLC: Fr 0,39 (cloroformo:metanol:agua = 8:2: 0,2); RMN: δ 8,05 (d, J = 8,1 Hz, 2H), 7,47 (d, J = 8,1 Hz, 2H), 7,08 (s, 1H), 6,93 (s, 1H), 6,80 (d, J = 3,3 Hz, 1H), 6,01 (m, 1H), 5,15-4,80 (a, 2H), 3,46 (d, J = 7,2 Hz, 2H), 2,27 (s, 3M, 2,19 (s, 3H), 1,64 (m, 1H), 0,88 (d, J = 6,9 Hz, 6H). TLC: Fr 0.39 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 8.05 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H), 7.08 (s, 1H), 6.93 (s, 1H), 6.80 (d, J = 3.3 Hz, 1H), 6.01 (m, 1H), 5.15-4.80 (a, 2H), 3.46 (d, J = 7.2 Hz, 2H), 2.27 (s, 3M, 2.19 (s, 3H), 1 , 64 (m, 1H), 0.88 (d, J = 6.9 Hz, 6H).

Ejemplo 3(4) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida Example 3 (4) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide

TLC: Fr 0,41 (cloroformo:metanol:agua = 8:2: 0,2); RMN (DMSOd6): δ 8,04 (d, J = 8,1 Hz, 2H), 7,66 (d, J = 8,1 Hz, 2H), 7,01 (s, 1H), 6,91 (d, J = 3,3 Hz, 1H), 6,76 (s, 1H), 6,29-6,23 (m, 1H), 5,18 y 5,12 (cada d, J = 13,5 Hz, cada 1H), 4,30 (sept, J = 6,6 Hz, 1H), 2,30 (s, 3H), 2,23 (s, 3H), 2,14 (s, 3H), 1,02 y 1,00 (cada d, J = 6,6 Hz, cada 3H). TLC: Fr 0.41 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSOd6): δ 8.04 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H), 7.01 (s, 1H), 6.91 (d, J = 3.3 Hz, 1H), 6.76 (s, 1H), 6.29-6.23 (m, 1H), 5.18 and 5.12 (every d, J = 13.5 Hz, every 1H), 4.30 (sept, J = 6.6 Hz , 1H), 2.30 (s, 3H), 2.23 (s, 3H), 2.14 (s, 3H), 1.02 and 1.00 (every d, J = 6.6 Hz, every 3H).

Ejemplo 3(5) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 3 (5) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

10 TLC: Fr 0,37 (cloroformo:metanol:agua = 8:2 : 0,2); RMN (DMSOd6): δ 8,04 (d, J = 8,4 Hz, 2H), 7,53 (d, J = 8,4 Hz, 2H), 6,96 (s, 1H), 6,92 (s, 1H), 6,82 (d, J = 3,3 Hz, 1H), 6,19-6,13 (m, 1H), 5,28-4,82 (m, 2H), 3,38 (d, J = 6,9 Hz, 2H), 2,21 (s, 3H), 2,14 (s, 6H), 1,64-1,44 (m, 1H), 0,85 (d, J = 6,6 Hz, 6H). 10 TLC: Fr 0.37 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSOd6): δ 8.04 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.92 (s, 1H), 6.82 (d, J = 3.3 Hz, 1H), 6.19-6.13 (m, 1H), 5.28-4.82 (m, 2H), 3, 38 (d, J = 6.9 Hz, 2H), 2.21 (s, 3H), 2.14 (s, 6H), 1.64-1.44 (m, 1H), 0.85 (d , J = 6.6 Hz, 6H).

15 Ejemplo 3(10) N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonamida Example 3 (10) N- [4-chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonamide

20 TLC: Fr 0,24 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 547 (M)+. TLC: Fr 0.24 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 547 (M) +.

Ejemplo 3(11) 25 N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 3 (11) N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

TLC: Fr 0,24 (diclorometano:metanol = 10:1); 30 EM (FAB, Pos.): 533 (M)+. TLC: Fr 0.24 (dichloromethane: methanol = 10: 1); 30 MS (FAB, Pos.): 533 (M) +.

Ejemplo 3(14) N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 3 (14) N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide

5 TLC: Fr 0,46 (cloroformo:metanol:agua = 8:2: 0,2); EM (FAB, Pos.): 527 (M + H)+. 5 TLC: Fr 0.46 (chloroform: methanol: water = 8: 2: 0.2); MS (FAB, Pos.): 527 (M + H) +.

Ejemplo 3(15) 10 N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 3 (15) 10 N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

TLC: Fr 0,52 (cloroformo:metanol:agua = 8:2 : 0,2); 15 EM (FAB, Pos.): 513 (M + H)+. TLC: Fr 0.52 (chloroform: methanol: water = 8: 2: 0.2); 15 MS (FAB, Pos.): 513 (M + H) +.

Ejemplo 3(16) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 3 (16) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

TLC: Fr 0,29 (cloroformo:metanol = 5:1); EM (APCI, Neg. 20V): 497 (M -H)-. TLC: Fr 0.29 (chloroform: methanol = 5: 1); MS (APCI, Neg. 20V): 497 (M-H) -.

25 Ejemplo 3(17) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 3 (17) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide

30 TLC: Fr 0,26 (cloroformo:metanol = 5:1); EM (APCI, Neg. 20V): 511 (M -H)-. TLC: Fr 0.26 (chloroform: methanol = 5: 1); MS (APCI, Neg. 20V): 511 (M-H) -.

Ejemplo 3(18) N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 3 (18) N- [4-chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

5 TLC: Fr 0,31 (cloroformo:metanol:agua = 8:2: 0,2); RMN: δ 8,02 (d, J = 8,4 Hz, 2H), 7,51 (d, J = 8,4 Hz, 2H), 7,10 (s, 1H), 6,98 (s, 2H), 5,03 y 4,95 (cada d, J = 12,6 Hz, cada 1H), 4,65 (sept, J = 6,6 Hz, 1H), 2,46 (s, 3H), 2,26 (s, 3H), 1,13 y 1,12 (cada d, J = 6,6 Hz, cada 3H). 5 TLC: Fr 0.31 (chloroform: methanol: water = 8: 2: 0.2); NMR: δ 8.02 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.10 (s, 1H), 6.98 (s, 2H), 5.03 and 4.95 (every d, J = 12.6 Hz, every 1H), 4.65 (Sept, J = 6.6 Hz, 1H), 2.46 (s, 3H), 2.26 (s, 3H), 1.13 and 1.12 (every d, J = 6.6 Hz, every 3H).

10 Ejemplo 3(19) N-[4-cloro.5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 3 (19) N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide

15 TLC: Fr 0,29 (cloroformo:metanol:agua = 8:2: 0,2); RMN (DMSO-d6): δ 8,05 (d, J = 8,4 Hz, 2H), 7,52 (s, 1H), 7,45 (d, J = 8,4 Hz, 2H), 7,26 (s, 1H), 7,25 (s, 1H), 5,254,73 (m, 2H), 3,62-3,40 (m, 2H), 2,26 (s, 3H), 2,22 (s, 3H), 1,66-1,50 (m, 1H), 0,88 (d, J = 6,6 Hz, 6H). TLC: Fr 0.29 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSO-d6): δ 8.05 (d, J = 8.4 Hz, 2H), 7.52 (s, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7 , 26 (s, 1H), 7.25 (s, 1H), 5,254.73 (m, 2H), 3.62-3.40 (m, 2H), 2.26 (s, 3H), 2, 22 (s, 3H), 1.66-1.50 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H).

Ejemplo 3(20) 20 N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 3 (20) 20 N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

TLC: Fr 0,31 (cloroformo:metanol = 5:1); TLC: Fr 0.31 (chloroform: methanol = 5: 1);

25 RMN (CDCI3 + 1 gota de CD3OD): δ 7,71 (d, J = 7,5 Hz, 1H), 7,70 (d, J = 1,5 Hz, 1H), 7,51 (dd, J = 7,5, 1,5 Hz, 1H), 7,07 (d, J = 0,9 Hz, 1H), 6,83 (s, 1H), 6,82 (s, 1H), 5,09 (d, J = 13,8 Hz, 1H), 5,04 (d, J = 13,8 Hz, 1H), 4,68 (m, 1H), 3,97 (s, 3H), 2,46 (d, J = 0,9 Hz, 3H), 2,25 (s, 3H), 2,16 (s, 3H), 1,15 (d, J = 6,6 Hz, 3H), 1,14 (d, J = 6,6 Hz, 3H). NMR (CDCI3 + 1 drop of CD3OD): δ 7.71 (d, J = 7.5 Hz, 1H), 7.70 (d, J = 1.5 Hz, 1H), 7.51 (dd, J = 7.5, 1.5 Hz, 1H), 7.07 (d, J = 0.9 Hz, 1H), 6.83 (s, 1H), 6.82 (s, 1H), 5, 09 (d, J = 13.8 Hz, 1H), 5.04 (d, J = 13.8 Hz, 1H), 4.68 (m, 1H), 3.97 (s, 3H), 2, 46 (d, J = 0.9 Hz, 3H), 2.25 (s, 3H), 2.16 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1, 14 (d, J = 6.6 Hz, 3H).

Ejemplo 3(26) N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 3 (26) N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

5 TLC: Fr 0,40 (cloroformo:metanol:agua = 8:2: 0,2); EM (FAB, Pos.): 507 (M + H)+. 5 TLC: Fr 0.40 (chloroform: methanol: water = 8: 2: 0.2); MS (FAB, Pos.): 507 (M + H) +.

Ejemplo 3(27) 10 N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida Example 3 (27) 10 N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide

TLC: Fr 0,44 (cloroformo:metanol:agua = 8:2: 0,2); 15 EM (FAB, Pos.): 507 (M + H)+. TLC: Fr 0.44 (chloroform: methanol: water = 8: 2: 0.2); 15 MS (FAB, Pos.): 507 (M + H) +.

Ejemplo 3(28) N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida Example 3 (28) N- [4-chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide

TLC: Fr 0,28 (cloroformo:metanol:agua = 8:2: 0,2); RMN (DMSO-d6): δ 8,69 (d, J = 1,8 Hz, 1H), 8,64 (dd, J = 4,8, 1,8 Hz, 1H), 8,00 (d, J = 8,1 Hz, 2H), 7,98-7,92 (m, 1H), 7,40 (dd, J = 8,1, 4,8 Hz, 1H), 7,30 (d, J = 8,4 Hz, 2H), 7,27 (s, 1H), 7,24 (s, 1H), 5,17-4,68 (m, 2H), 3,46-3,16 TLC: Fr 0.28 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSO-d6): δ 8.69 (d, J = 1.8 Hz, 1H), 8.64 (dd, J = 4.8, 1.8 Hz, 1H), 8.00 (d, J = 8.1 Hz, 2H), 7.98-7.92 (m, 1H), 7.40 (dd, J = 8.1, 4.8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.27 (s, 1H), 7, 24 (s, 1H), 5.17-4.68 (m, 2H), 3.46-3.16

25 (m, 2H), 2,28 (s, 3H), 1,60-1,42 (m, 1H), 1,00-0,73 (m, 6H). 25 (m, 2H), 2.28 (s, 3H), 1.60-1.42 (m, 1H), 1.00-0.73 (m, 6H).

Ejemplo 3(29) N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 3 (29) N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

5 TLC: Fr 0,22 (cloroformo:metanol:agua = 40:10:1); RMN: δ 8,52 (d, J = 4,5 Hz, 1H), 8,20 (d, J = 1,5 Hz, 1H), 7,98 (d, J = 7,8 Hz, 1H), 7,79 (dt, J = 1,5, 8,1 Hz, 1H), 7,71 (d, J = 8,1 Hz, 1H), 7,47 (d, J = 7,8 Hz, 1H), 7,35-7,30 (m, 1H), 7,04 (s, 1H), 6,63 (s, 1H), 4,90 (a, 1H), 4,64 (a, 1H), 3,67 (a, 1H), 3,57 (a, 1H), 2,21 (s, 3H), 2,15 (s, 3H), 1,80-1,60 (m, 1H), 0,91 (a, 6H). 5 TLC: Fr 0.22 (chloroform: methanol: water = 40: 10: 1); NMR: δ 8.52 (d, J = 4.5 Hz, 1H), 8.20 (d, J = 1.5 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H) , 7.79 (dt, J = 1.5, 8.1 Hz, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.35-7.30 (m, 1H), 7.04 (s, 1H), 6.63 (s, 1H), 4.90 (a, 1H), 4.64 (a, 1H ), 3.67 (a, 1H), 3.57 (a, 1H), 2.21 (s, 3H), 2.15 (s, 3H), 1.80-1.60 (m, 1H) , 0.91 (a, 6H).

10 Ejemplo 3(30) N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-3-piridilsulfonilamida Example 3 (30) N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-3-pyridylsulfonylamide

15 TLC: Fr 0,22 (cloroformo:metanol:agua = 40:10:1); RMN: δ 9,11 (d, J = 1,8 Hz, 1H), 8,61 (dd, J = 4,8, 1,5 Hz, 1H), 8,20-8,10 (m, 2H), 7,88 (dd, J = 7,8, 1,5 Hz, 1H), 7,42 (dd, J = 8,1, 4,8 Hz, 1H), 7,33 (d, J = 7,8 Hz, 1H), 7,01 (s, 1H), 6,79 (s, 1H), 4,96 (d, J = 13,5 Hz, 1H), 4,93 (d, J = 13,5 Hz, 1H), 4,60-4,45 (m, 1H), 2,29 (s, 3H), 2,23 (s, 3H), 1,25 (d, J = 6,6 Hz, 3H), 1,11 (d, J = 6,6 Hz, 3H). TLC: Fr 0.22 (chloroform: methanol: water = 40: 10: 1); NMR: δ 9.11 (d, J = 1.8 Hz, 1H), 8.61 (dd, J = 4.8, 1.5 Hz, 1H), 8.20-8.10 (m, 2H ), 7.88 (dd, J = 7.8, 1.5 Hz, 1H), 7.42 (dd, J = 8.1, 4.8 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.01 (s, 1H), 6.79 (s, 1H), 4.96 (d, J = 13.5 Hz, 1H), 4.93 (d, J = 13.5 Hz, 1H), 4.60-4.45 (m, 1H), 2.29 (s, 3H), 2.23 (s, 3H), 1.25 (d, J = 6.6 Hz, 3H), 1.11 (d, J = 6.6 Hz, 3H).

20 Ejemplo 3(31) N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida Example 3 (31) N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide

25 TLC: Fr 0,22 (cloroformo:metanol:agua = 40:10:1); RMN: δ 8,97(d, J = 1,8 Hz, 1H), 8,55-8,45 (m, 1H), 8,15(d, J = 1,5 Hz, 1H), 7,89 (d, J = 7,8 Hz, 1H), 7,8 (dt, J = 8,1, 1,8 Hz, 1H), 7,31 (dd, J = 8,1, 4,8 Hz, 1H), 7,24 (s, 1H), 7,07 (d, J = 7,8 Hz, 1H), 6,75 (s, 1H), 4,89 (d, J = 12,5 Hz, 1H), 4,63 (d, J = 12,5 Hz, 1H), 3,70-3,60 (m, 1H), 3,45-3,30 (m, 1M, 2,30 (s, 3H), 2,26 (s, 3H), 1,80-1,60 (m, 1H), J = 25 TLC: Fr 0.22 (chloroform: methanol: water = 40: 10: 1); NMR: δ 8.97 (d, J = 1.8 Hz, 1H), 8.55-8.45 (m, 1H), 8.15 (d, J = 1.5 Hz, 1H), 7, 89 (d, J = 7.8 Hz, 1H), 7.8 (dt, J = 8.1, 1.8 Hz, 1H), 7.31 (dd, J = 8.1, 4.8 Hz , 1H), 7.24 (s, 1H), 7.07 (d, J = 7.8 Hz, 1H), 6.75 (s, 1H), 4.89 (d, J = 12.5 Hz , 1H), 4.63 (d, J = 12.5 Hz, 1H), 3.70-3.60 (m, 1H), 3.45-3.30 (m, 1M, 2.30 (s , 3H), 2.26 (s, 3H), 1.80-1.60 (m, 1H), J =

30 6,6 Hz, 3H), 0,93 (d, J = 6,6 Hz, 3H). 30 6.6 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H).

Ejemplo 3(32) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil)-N-isopropil-2-piridilsulfonilamida Example 3 (32) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl) -N-isopropyl-2-pyridylsulfonylamide

5 TLC: Fr 0,23 (cloroformo:metanol = 5:1); EM (APCI, Neg. 20V): 477 (M -H)-. 5 TLC: Fr 0.23 (chloroform: methanol = 5: 1); MS (APCI, Neg. 20V): 477 (M-H) -.

Ejemplo 3 (33) 10 N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 3 (33) 10 N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

TLC: Fr 0,23 (cloroformo:metanol = 5:1); 15 EM (APCI, Neg. 20V): 491 (M -H)-. TLC: Fr 0.23 (chloroform: methanol = 5: 1); 15 MS (APCI, Neg. 20V): 491 (M-H) -.

Ejemplo 3(34) N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida Example 3 (34) N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide

TLC: Fr 0,23 (cloroformo:metanol = 5:1); EM (APCI, Neg. 20V): 491 (M -H)-. TLC: Fr 0.23 (chloroform: methanol = 5: 1); MS (APCI, Neg. 20V): 491 (M-H) -.

25 Ejemplo 3(35) N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida Example 3 (35) N- [4-chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide

30 TLC: Fr 0,30 (cloroformo:metanol:agua = 8:2: 0,2); TLC: Fr 0.30 (chloroform: methanol: water = 8: 2: 0.2);

RMN (DMSOd6): δ 8,67 (d, J = 3,6 Hz, 1H), 7,98-7,88 (m, 2H), 7,85-7,78 (m, 2H), 7,55-7,48 (m, 2H), 7,37 (s, 1H), 7,04 (s, 1H), 5,10 (ABd, J = 13,2 Hz) y 5,04 (ABd, J = 13,2 Hz) total 2H, 4,49 (sept, J = 6,9 Hz, 1H), 2,36 (s, 3H), 2,23 (s, 3H), 1,02 (d, J = 6,9 Hz) y 0,99 (d, J = 6,9 Hz) total 6H. NMR (DMSOd6): δ 8.67 (d, J = 3.6 Hz, 1H), 7.98-7.88 (m, 2H), 7.85-7.78 (m, 2H), 7, 55-7.48 (m, 2H), 7.37 (s, 1H), 7.04 (s, 1H), 5.10 (ABd, J = 13.2 Hz) and 5.04 (ABd, J = 13.2 Hz) total 2H, 4.49 (sept, J = 6.9 Hz, 1H), 2.36 (s, 3H), 2.23 (s, 3H), 1.02 (d, J = 6.9 Hz) and 0.99 (d, J = 6.9 Hz) total 6H.

Ejemplo 3(36) N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 3 (36) N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

10 TLC: Fr 0,26 (cloroformo:metanol:agua = 8: 2 : 0,2); RMN (DMSO-d6): δ 8,48 (m, 1H), 7,93-7,85 (m) y 7,90 (dd, J = 7,8, 1,8 Hz) total 2H, 7,8 (d, J = 8,1 Hz, 1H), 7,68 (d, J = 8,1 Hz, 1H), 7,44 (ddd, J = 7,8, 4,8, 1,2 Hz, 1H), 7,29 (s) y 7,27 (d, J = 7,8 Hz) total 2H, 7,20 (s, 1H), 4,92 (m, 2H), 3,47 (m, 2H), 2,31 (s, 3H), 2,23 (s, 3H), 1,50 (m, 1H), 0,81 (d, J = 6,6 Hz, 6H). TLC: Fr 0.26 (chloroform: methanol: water = 8: 2: 0.2); NMR (DMSO-d6): δ 8.48 (m, 1H), 7.93-7.85 (m) and 7.90 (dd, J = 7.8, 1.8 Hz) total 2H, 7, 8 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.44 (ddd, J = 7.8, 4.8, 1.2 Hz , 1H), 7.29 (s) and 7.27 (d, J = 7.8 Hz) total 2H, 7.20 (s, 1H), 4.92 (m, 2H), 3.47 (m , 2H), 2.31 (s, 3H), 2.23 (s, 3H), 1.50 (m, 1H), 0.81 (d, J = 6.6 Hz, 6H).

15 Ejemplo 3(37) N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 3 (37) N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

20 TLC: Fr 0,23 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 523 (M + H)+. TLC: Fr 0.23 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 523 (M + H) +.

Ejemplo 3(38) N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida 25 Example 3 (38) N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide 25

TLC: Fr 0,23 (cloroformo:metanol = 10:1); TLC: Fr 0.23 (chloroform: methanol = 10: 1);

Ejemplo de Referencia 5 N-[4,5-dimetil-2-[2-metil-4-(N-hidroxiamidino)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Reference Example 5 N- [4,5-dimethyl-2- [2-methyl-4- (N-hydroxyamidino) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

5 A una solución de N-[4,5-dimetil-2-(2-metil-4-cianofenilmetiloxi)fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida preparada en el Ejemplo de Referencia 4 (70 mg) en etanol (2 ml), se le añadieron trietilamina (42 μl) y sal cloruro de hidrógeno de hidroxilamina (21 mg) a temperatura ambiente y después la mezcla se calentó a reflujo durante 5 horas. Después de que se completara la reacción, la mezcla de reacción se vertió en acetato de etilo-agua. La fase 5 To a solution of N- [4,5-dimethyl-2- (2-methyl-4-cyanophenylmethyloxy) phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide prepared in Reference Example 4 ( 70 mg) in ethanol (2 ml), triethylamine (42 μl) and hydroxylamine hydrogen chloride salt (21 mg) were added at room temperature and then the mixture was heated at reflux for 5 hours. After the reaction was completed, the reaction mixture was poured into ethyl acetate-water. The phase

10 orgánica se lavó, se secó y se concentró a presión reducida para dar el compuesto del título (80 mg) que tenía los siguientes datos físicos. TLC: Fr 0,38 (n-hexano:acetato de etilo = 2:3). The organic was washed, dried and concentrated under reduced pressure to give the title compound (80 mg) having the following physical data. TLC: Fr 0.38 (n-hexane: ethyl acetate = 2: 3).

Ejemplo 4 15 N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 4 N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5- methyl-2-furyl) sulfonylamide

A una solución de N-[4,5-dimetil-2-[2-metil-4-(N-hidroxiamidino)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2To a solution of N- [4,5-dimethyl-2- [2-methyl-4- (N-hydroxyamidino) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2

20 furil)sulfonilamida preparada den el Ejemplo de Referencia 5 (78 mg) en N,N-dimetilformamida (1 ml), Se le añadieron piridina (16 μl) y 2-etilhexil éster del ácido clorofórmico (30 μI) y la mezcla se agitó durante 1 hora a 0 ºC. Después de que se completara la reacción, la mezcla de reacción se vertió en acetato de etilo-agua. La fase orgánica se lavó, se secó y se concentró a presión reducida. Al residuo, se le añadieron xilenos (2 ml) y la mezcla se calentó a reflujo durante 6 horas a 140 ºC. Después de que se completara la reacción, la mezcla de reacción se 20 furyl) sulfonyl amide prepared in Reference Example 5 (78 mg) in N, N-dimethylformamide (1 ml), pyridine (16 μl) and 2-ethylhexyl ester of chloroformic acid (30 μI) were added and the mixture was stirred for 1 hour at 0 ° C. After the reaction was completed, the reaction mixture was poured into ethyl acetate-water. The organic phase was washed, dried and concentrated under reduced pressure. To the residue, xylenes (2 ml) were added and the mixture was heated at reflux for 6 hours at 140 ° C. After the reaction was completed, the reaction mixture was

25 concentró a presión reducida. El residuo se purificó por cromatografía en columna sobre gel de sílice (hexanoacetato de etilo), dando el compuesto del título (42 mg) que tenía los siguientes datos físicos. TLC: Fr 0,43 (cloroformo:metanol = 19:1); RMN: δ 10,69 (a, 1H), 7,62 (s, 1H), 7,59 (d, J = 8,1 Hz, 1H), 7,54 (d, J = 8,1 Hz, 1H), 6,97 (s, 1H), 6,78 (d, J = 3,3 Hz, 1H), 6,71 (s, 1H), 6,00 (d, J = 3,3 Hz, 1H), 4,94 (a, 2H), 3,46 (d, J = 7,5 Hz, 2H), 2,39 (s, 3H), 2,24 (s, 3H), 2,19 (s, 25 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl hexane acetate) to give the title compound (42 mg) that had the following physical data. TLC: Fr 0.43 (chloroform: methanol = 19: 1); NMR: δ 10.69 (a, 1H), 7.62 (s, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 6.97 (s, 1H), 6.78 (d, J = 3.3 Hz, 1H), 6.71 (s, 1H), 6.00 (d, J = 3.3 Hz, 1H), 4.94 (a, 2H), 3.46 (d, J = 7.5 Hz, 2H), 2.39 (s, 3H), 2.24 (s, 3H), 2.19 ( s,

30 3H), 2,18 (s, 3H), 1,70-1,55 (m, 1H), 0,89 (d, J = 6,6 Hz, 6H). 30 3H), 2.18 (s, 3H), 1.70-1.55 (m, 1H), 0.89 (d, J = 6.6 Hz, 6H).

Mediante los mismos procedimientos que se han descrito en los Ejemplos de Referencia 1 a 5 y el Ejemplo 4, se obtuvieron los compuestos que tienen los siguientes datos físicos. By the same procedures as described in Reference Examples 1 to 5 and Example 4, the compounds having the following physical data were obtained.

Ejemplo 4(1) N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida Example 4 (1) N- [4-chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5- methyl-2-furyl) sulfonylamide

5 TLC: Fr 0,40 (cloroformo:metanol = 19:1); RMN: δ 10,81 (a, 1H), 7,79 (d, J = 8,3 Hz, 2H), 7,63 (d, J = 8,3 Hz, 2H), 6,97 (s, 1H), 6,92 (s, 1H), 6,84 (d, J = 3,3 Hz, 1H), 6,10-6,00 (m, 1H), 5,07 (s, 2H), 4,55-4,35 (m, 1H), 2,34 (s, 3H), 2,28 (s, 3H), 1,10 (d, J = 6,6 Hz, 3H), 1,07 (d, J = 6,6 Hz, 3H). 5 TLC: Fr 0.40 (chloroform: methanol = 19: 1); NMR: δ 10.81 (a, 1H), 7.79 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 6.97 (s, 1H), 6.92 (s, 1H), 6.84 (d, J = 3.3 Hz, 1H), 6.10-6.00 (m, 1H), 5.07 (s, 2H), 4.55-4.35 (m, 1H), 2.34 (s, 3H), 2.28 (s, 3H), 1.10 (d, J = 6.6 Hz, 3H), 1.07 (d, J = 6.6 Hz, 3H).

10 Ejemplo 4(2) N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 4 (2) N- [4-chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5 -methyl-2-furyl) sulfonylamide

15 TLC: Fr 0,38 (cloroformo:metanol = 19:1); RMN: δ 11,01 (a, 1H), 7,80 (d, J = 8,3 Hz, 2H), 7,52 (d, J = 8,3 Hz, 2H), 7,10 (s, 1H), 6,92 (s, 1H), 6,78 (d, J = 3,3 Hz, 1H), 6,05-5,95 (m, 1H), 5,02 (a, 2H), 3,45 (d, J = 7,2 Hz, 2H), 2,29 (s, 3H), 2,20 (s, 3H), 1,70-1,55 (m, 1H), 0,90 (d, J = 6,9 Hz, 6H). TLC: Fr 0.38 (chloroform: methanol = 19: 1); NMR: δ 11.01 (a, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.10 (s, 1H), 6.92 (s, 1H), 6.78 (d, J = 3.3 Hz, 1H), 6.05-5.95 (m, 1H), 5.02 (a, 2H), 3.45 (d, J = 7.2 Hz, 2H), 2.29 (s, 3H), 2.20 (s, 3H), 1.70-1.55 (m, 1H), 0.90 (d, J = 6.9 Hz, 6H).

20 Ejemplo 4(3) N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida Example 4 (3) N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide

25 TLC: Fr 0,43 (cloroformo:metanol = 19:1); RMN: δ 10,34 (a, 1H), 7,71 (d, J = 8,1 Hz, 1H), 7,65-7,55 (m, 2H), 6,86 (d, J = 3,3 Hz, 1H), 6,79 (s, 1H), 6,74 (s, 1H), 6,10-6,05 (m, 1H), 4,93 (s, 2H), 4,50-4,40 (m, 1H), 2,37 (s, 3H), 2,34 (s, 3H), 2,26 (s, 3H), 2,17 (s, 3H), 1,09 (d, J = 6,6 Hz, 3H), 1,07 (d, J = 6,6 Hz, 3H). TLC: Fr 0.43 (chloroform: methanol = 19: 1); NMR: δ 10.34 (a, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.65-7.55 (m, 2H), 6.86 (d, J = 3 , 3 Hz, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 6.10-6.05 (m, 1H), 4.93 (s, 2H), 4.50 -4.40 (m, 1H), 2.37 (s, 3H), 2.34 (s, 3H), 2.26 (s, 3H), 2.17 (s, 3H), 1.09 ( d, J = 6.6 Hz, 3H), 1.07 (d, J = 6.6 Hz, 3H).

30 Ejemplo 4(4) N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 4 (4) N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl -2-furyl) sulfonylamide

5 TLC: Fr 0,53 (cloroformo:metanol = 9:1); RMN: δ 11,10-10,50 (a, 1H, NH), 7,78 (d, J = 8,7 Hz, 2H), 7,52 (d, J = 8,7 Hz, 2H), 6,97 (s, 1H), 6,78 (d, J = 3,3 Hz, 1H), 6,69 (s, 1H), 6,01-5,98 (m, 1H), 5,15-4,85 (m, 2H), 3,46 (d, J = 7,2 Hz, 2H), 2,22 (s, 3H), 2,20 (s, 3H), 2,17 (s, 3H), 1,73-1,60 (m, 1H), 0,90 (d, J = 6,9 Hz, 6H). 5 TLC: Fr 0.53 (chloroform: methanol = 9: 1); NMR: δ 11.10-10.50 (a, 1H, NH), 7.78 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8.7 Hz, 2H), 6.97 (s, 1H), 6.78 (d, J = 3.3 Hz, 1H), 6.69 (s, 1H), 6.01-5.98 (m, 1H), 5.15 -4.85 (m, 2H), 3.46 (d, J = 7.2 Hz, 2H), 2.22 (s, 3H), 2.20 (s, 3H), 2.17 (s, 3H), 1.73-1.60 (m, 1H), 0.90 (d, J = 6.9 Hz, 6H).

10 Ejemplo 4(5) N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida Example 4 (5) N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide

15 TLC: Fr 0,46 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 542 (M + H)+. TLC: Fr 0.46 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 542 (M + H) +.

Ejemplo 4(6) 20 N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida Example 4 (6) 20 N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide

TLC: Fr 0,44 (diclorometano:metanol = 19:1); TLC: Fr 0.44 (dichloromethane: methanol = 19: 1);

25 RMN: δ 7,68 (d, J = 8,1 Hz, 1H), 7,35 (dd, J = 8,1, 1,5 Hz, 1H), 7,24 (d, J = 1,5 Hz, 1H), 6,91 (d, J = 3,3 Hz, 1H), 6,77 (s, 1H), 6,72 (s, 1H), 6,11 (dd, J = 3,3, 0,6 Hz, 1H), 4,92 (d, J = 14,7 Hz, 1H), 4,83 (d, J = 14,7 Hz, 1H), 4,49 (m, 1H), 3,93 (s, 3H), 2,37 (s, 3H), 2,25 (s, 3H), 2,17 (s, 3H), 1,09 (d, J = 6,9 Hz, 3H), 1,07 (d, J = 6,9 Hz, 3H). NMR: δ 7.68 (d, J = 8.1 Hz, 1H), 7.35 (dd, J = 8.1, 1.5 Hz, 1H), 7.24 (d, J = 1, 5 Hz, 1H), 6.91 (d, J = 3.3 Hz, 1H), 6.77 (s, 1H), 6.72 (s, 1H), 6.11 (dd, J = 3, 3, 0.6 Hz, 1H), 4.92 (d, J = 14.7 Hz, 1H), 4.83 (d, J = 14.7 Hz, 1H), 4.49 (m, 1H) , 3.93 (s, 3H), 2.37 (s, 3H), 2.25 (s, 3H), 2.17 (s, 3H), 1.09 (d, J = 6.9 Hz, 3H), 1.07 (d, J = 6.9 Hz, 3H).

Ejemplo 4(10) N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 4 (10) N- [4-chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4- methyl-2-thiazolyl) sulfonylamide

5 TLC: Fr 0,37 (cloroformo:metanol = 19:1); RMN: δ 10,89 (a, 1H), 7,79 (d, J = 8,4 Hz, 2H), 7,44 (d, J = 8,4 Hz, 2H), 7,17 (s, 1H), 7,01 (s, 1H), 6,92 (s, 1H), 4,99 (a, 1H), 4,87 (a, 1H), 3,57 (a, 2H), 2,36 (s, 3H), 2,27 (s, 3H), 1,80-1,60 (m, 1H), 0,93 (d, J = 6,6 Hz, 6H). 5 TLC: Fr 0.37 (chloroform: methanol = 19: 1); NMR: δ 10.89 (a, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.17 (s, 1H), 7.01 (s, 1H), 6.92 (s, 1H), 4.99 (a, 1H), 4.87 (a, 1H), 3.57 (a, 2H), 2, 36 (s, 3H), 2.27 (s, 3H), 1.80-1.60 (m, 1H), 0.93 (d, J = 6.6 Hz, 6H).

10 Ejemplo 4(11) N-[4-cloro-5-metil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 4 (11) N- [4-chloro-5-methyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N- isobutyl- (4-methyl-2-thiazolyl) sulfonylamide

15 TLC: Fr 0,43 (acetato de etilo); RMN (DMSOd6): δ 7,67 (s, 1H), 7,64 (d, J = 8,1 Hz, 1H), 7,50 (s, 1H), 7,34 (s, 1H), 7,32 (d, J = 8,1 Hz, 1H), 7,21 (s, 1H), 5,06 (s a, 1H), 4,87 (s a, 1H), 3,45 (s a, 2H), 2,33 (s, 3H), 2,27 (s, 3H), 2,22 (s, 3H), 1,70-1,50 (m, 1H), 0,86 (d a, J = 6,3 Hz, 6H). TLC: Fr 0.43 (ethyl acetate); NMR (DMSOd6): δ 7.67 (s, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.50 (s, 1H), 7.34 (s, 1H), 7 , 32 (d, J = 8.1 Hz, 1H), 7.21 (s, 1H), 5.06 (sa, 1H), 4.87 (sa, 1H), 3.45 (sa, 2H) , 2.33 (s, 3H), 2.27 (s, 3H), 2.22 (s, 3H), 1.70-1.50 (m, 1H), 0.86 (da, J = 6 , 3 Hz, 6H).

20 Ejemplo 4(13) N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 4 (13) N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide

25 TLC: Fr 0,45 (cloroformo:metanol = 19:1); RMN: δ 10,95 (a, 1H), 7,62 (s, 1H), 7,59 (d, J = 8,1 Hz, 1H), 7,40 (d, J = 8,1 Hz, 1H), 7,03 (s, 1H), 6,99 (s, 1H), 6,71 (s, 1H), 4,91 (a, 1H), 4,82 (a, 1H), 3,57 (a, 2H), 2,37 (s, 3H), 2,34 (s, 3H), 2,24 (s, 3H), 2,17 (s, 3H), 1,80-1,60 (m, 1H), 0,93 (a, 6H). 25 TLC: Fr 0.45 (chloroform: methanol = 19: 1); NMR: δ 10.95 (a, 1H), 7.62 (s, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H), 6.99 (s, 1H), 6.71 (s, 1H), 4.91 (a, 1H), 4.82 (a, 1H), 3, 57 (a, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.24 (s, 3H), 2.17 (s, 3H), 1.80-1.60 (m, 1H), 0.93 (a, 6H).

Ejemplo 4(14) N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 4 (14) N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl- 2-thiazolyl) sulfonylamide

5 TLC: Fr 0,42 (cloroformo:metanol = 10:1); RMN: δ 7,77 (d, J = 8,4 Hz, 2H), 7,57 (d, J = 8,4 Hz, 2H), 7,06 (d, J = 0,9 Hz, 1H), 6,83 (s, 1H), 6,74 (s, 1H), 5,05 (d, J = 12,9 Hz, 1H), 5,00 (d, J = 12,9 Hz, 1H), 4,68 (m, 1H),2,49 (d, J = 0,9 Hz, 3H), 2,24 (s, 3H), 2,15 (s, 3H), 1,15 (d, J = 6,6 Hz, 3H), 1,13 (d, J = 6,6 Hz, 3H). 5 TLC: Fr 0.42 (chloroform: methanol = 10: 1); NMR: δ 7.77 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 0.9 Hz, 1H) , 6.83 (s, 1H), 6.74 (s, 1H), 5.05 (d, J = 12.9 Hz, 1H), 5.00 (d, J = 12.9 Hz, 1H) , 4.68 (m, 1H), 2.49 (d, J = 0.9 Hz, 3H), 2.24 (s, 3H), 2.15 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H).

10 Ejemplo 4(15) N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida Example 4 (15) N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl -2-thiazolyl) sulfonylamide

15 TLC: Fr 0,39 (cloroformo:metanol = 10:1); RMN: δ 7,78 (d, J = 8,4 Hz, 2H), 7,43 (d, J = 8,4 Hz, 2H), 7,03 (s, 1H), 6,97 (d, J = 0,9 Hz, 1H), 6,68 (s, 1H), 5,124,68 (m, 2H), 3,73-3,42 (m, 2H), 2,35 (d, J = 0,9 Hz, 3H), 2,23 (s, 3H), 2,17 (s, 3H), 1,69 (m, 1H), 1,03-0,86 (m, 6H). TLC: Fr 0.39 (chloroform: methanol = 10: 1); NMR: δ 7.78 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.03 (s, 1H), 6.97 (d, J = 0.9 Hz, 1H), 6.68 (s, 1H), 5,124.68 (m, 2H), 3.73-3.42 (m, 2H), 2.35 (d, J = 0 , 9 Hz, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 1.69 (m, 1H), 1.03-0.86 (m, 6H).

20 Ejemplo 4(16) N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida Example 4 (16) N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide

25 TLC: Fr 0,37 (diclorometano : metanol =19:1); RMN: δ 7,63 (d, J = 7,8 Hz, 1H), 7,33 (dd, J = 7,8, 1,5 Hz, 1H), 7,30 (d, J = 1,5 Hz, 1H), 7,08 (s a, 1H), 6,83 (s, 1H), 6,76 (s, 1H), 5,02 (d, J = 14,4 Hz, 1H), 4,93 (d, J = 14,4 Hz, 1H), 4,69 (m, 1H), 3,93 (s, 3H), 2,49 (d, J = 1,2 Hz, 3H), 2,25 (s, 3H), 2,16 (s, 3H), 1,14 (d, J = 6,9 Hz, 3H), 1,13 (d, J = 6,9 Hz, 3H). 25 TLC: Rf 0.37 (dichloromethane: methanol = 19: 1); NMR: δ 7.63 (d, J = 7.8 Hz, 1H), 7.33 (dd, J = 7.8, 1.5 Hz, 1H), 7.30 (d, J = 1.5 Hz, 1H), 7.08 (sa, 1H), 6.83 (s, 1H), 6.76 (s, 1H), 5.02 (d, J = 14.4 Hz, 1H), 4, 93 (d, J = 14.4 Hz, 1H), 4.69 (m, 1H), 3.93 (s, 3H), 2.49 (d, J = 1.2 Hz, 3H), 2, 25 (s, 3H), 2.16 (s, 3H), 1.14 (d, J = 6.9 Hz, 3H), 1.13 (d, J = 6.9 Hz, 3H).

Ejemplo 4(18) N-[4-trifluorometil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 4 (18) N- [4-trifluoromethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide

5 TLC: Fr 0,46 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 8,60-8,50 (m, 1H), 7,90 (dt, J = 1,8, 7,8 Hz, 1H), 7,81 (d, J = 8,4 Hz, 2H), 7,72 (d, J = 7,5 Hz, 1H), 7,55-7,35 (m, 6H), 5,08 (s a, 2H), 3,52 (d a, J = 7,5 Hz, 2H), 1,60-1,40 (m, 1H), 0,83 (d, J = 6,6 Hz, 6H). 5 TLC: Fr 0.46 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 8.60-8.50 (m, 1H), 7.90 (dt, J = 1.8, 7.8 Hz, 1H), 7.81 (d, J = 8 , 4 Hz, 2H), 7.72 (d, J = 7.5 Hz, 1H), 7.55-7.35 (m, 6H), 5.08 (sa, 2H), 3.52 (da , J = 7.5 Hz, 2H), 1.60-1.40 (m, 1H), 0.83 (d, J = 6.6 Hz, 6H).

10 Ejemplo 4(19) N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida Example 4 (19) N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- 2-pyridylsulfonylamide

15 TLC: Fr 0,33 (cloroformo:metanol = 19:1); RMN: δ 10,41 (a, 1H), 8,75-8,70 (m, 1H), 7,90 (dd, J = 7,8, 0,9 Hz, 1H), 7,80 (dt, J = 0,9, 7,8 Hz, 1H), 7,65-7,50 (m, 3H), 7,41 (ddd, J = 7,8, 4,8, 0,9 Hz, 1H), 6,78 (s, 1H), 6,72 (s, 1H), 4,87 (d, J = 13,4 Hz, 1H), 4,83 (d, J = 13,4 Hz, 1H), 4,75-4,60 (m, 1H), 2,34 (s, 3H), 2,25 (s, 3H), 2,13 (s, 3H), 1,10 (d, J = 6,6 Hz, 6H). TLC: Fr 0.33 (chloroform: methanol = 19: 1); NMR: δ 10.41 (a, 1H), 8.75-8.70 (m, 1H), 7.90 (dd, J = 7.8, 0.9 Hz, 1H), 7.80 (dt , J = 0.9, 7.8 Hz, 1H), 7.65-7.50 (m, 3H), 7.41 (ddd, J = 7.8, 4.8, 0.9 Hz, 1H ), 6.78 (s, 1H), 6.72 (s, 1H), 4.87 (d, J = 13.4 Hz, 1H), 4.83 (d, J = 13.4 Hz, 1H ), 4.75-4.60 (m, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 2.13 (s, 3H), 1.10 (d, J = 6.6 Hz, 6H).

20 Ejemplo 4(20) N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida Example 4 (20) N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- 3-pyridylsulfonylamide

25 TLC: Fr 0,30 (cloroformo:metanol = 19: 1); RMN: δ 11,28 (a, 1H), 8,84 (d, J = 1,8 Hz, 1H), 8,49 (dd, J = 4,8, 1,8 Hz, 1H), 7,87 (dt, J = 8,1, 1,8 Hz, 1H), 7,62 (s, 1H), 7,47 (d, J = 7,8 Hz, 1H), 7,19 (dd, J = 8,1, 4,8 Hz, 1H), 7,15 (s, 1H), 6,97 (d, J = 7,8 Hz, 1H), 6,69 (s, 1H), 4,82 (a, 1H), 4,62 (a, 1H), 3,53 (a, 1H), 3,34 (a, 1H), 2,30 (s, 3H), 2,27 (s, 3H), 2,22 (s, 3H), 1,80-1,60 (m, 1H), 1,00 (a, 3H), 0,87 (a, 3H). 25 TLC: Fr 0.30 (chloroform: methanol = 19: 1); NMR: δ 11.28 (a, 1H), 8.84 (d, J = 1.8 Hz, 1H), 8.49 (dd, J = 4.8, 1.8 Hz, 1H), 7, 87 (dt, J = 8.1, 1.8 Hz, 1H), 7.62 (s, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.19 (dd, J = 8.1, 4.8 Hz, 1H), 7.15 (s, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.69 (s, 1H), 4.82 (a, 1H), 4.62 (a, 1H), 3.53 (a, 1H), 3.34 (a, 1H), 2.30 (s, 3H), 2.27 (s, 3H) , 2.22 (s, 3H), 1.80-1.60 (m, 1H), 1.00 (a, 3H), 0.87 (a, 3H).

30 Ejemplo 4(21) N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida Example 4 (21) N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- 2-pyridylsulfonylamide

5 TLC: Fr 0,36 (diclorometano:metanol = 10:1); EM (FAB, Pos.): 539 (M + H)+. 5 TLC: Rf 0.36 (dichloromethane: methanol = 10: 1); MS (FAB, Pos.): 539 (M + H) +.

Ejemplo 4(22) 10 N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida Example 4 (22) 10 N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- 2-pyridylsulfonylamide

TLC: Fr 0,37 (diclorometano:metanol = 19: 1); TLC: Fr 0.37 (dichloromethane: methanol = 19: 1);

15 RMN: δ 8,73 (ddd, J = 4,8, 1,5, 0,9 Hz, 1H), 7,91 (ddd, J = 7,8, 1,2, 0,9 Hz, 1H), 7,82 (ddd, J = 7,8, 7,8, 1,5 Hz, 1H), 7,57 (d, J = 7,8 Hz, 1H), 7,43 (ddd, J = 7,8, 4,8, 1,2 Hz, 1H), 7,32 (dd, J = 7,8, 1,5 Hz, 1H), 7,26 (m, 1H), 6,76 (s, 1H), 6,72 (s, 1H), 4,88 (d, J = 14,1 Hz, 1H), 4,78 (d, J = 14,1 Hz, 1H), 4,71 (m, 1H), 3,91 (s, 3H), 2,24 (s, 3H), 2,13 (s, 3H), 1,10 (d, J = 6,6 Hz, 3H), 1,09 (d, J = 6,6 Hz, 3H). 15 NMR: δ 8.73 (ddd, J = 4.8, 1.5, 0.9 Hz, 1H), 7.91 (ddd, J = 7.8, 1.2, 0.9 Hz, 1H ), 7.82 (ddd, J = 7.8, 7.8, 1.5 Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.43 (ddd, J = 7.8, 4.8, 1.2 Hz, 1H), 7.32 (dd, J = 7.8, 1.5 Hz, 1H), 7.26 (m, 1H), 6.76 (s , 1H), 6.72 (s, 1H), 4.88 (d, J = 14.1 Hz, 1H), 4.78 (d, J = 14.1 Hz, 1H), 4.71 (m , 1H), 3.91 (s, 3H), 2.24 (s, 3H), 2.13 (s, 3H), 1.10 (d, J = 6.6 Hz, 3H), 1.09 (d, J = 6.6 Hz, 3H).

20 Mediante el mismo procedimiento que se ha descrito en los Ejemplos de Referencia 1 a 3 y el Ejemplo 2, se obtuvieron los compuestos de la presente invención que tenían los siguientes datos físicos. By the same procedure as described in Reference Examples 1 to 3 and Example 2, the compounds of the present invention having the following physical data were obtained.

Ejemplo 5(2)Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]indan-5-iloximetil]benzoico 25 Example 5 (2) 3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,54 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,80-7,70 (m, 2H), 7,37 (d, J = 7,8 Hz, 1H), 7,05 (s, 1H), 6,99 (s, 1H), 6,87 (d, J = 3,3 Hz, 1H), 30 6,17 (d, J = 3,3 Hz, 1H), 4,99 (a, 2H), 4,72 (s, 2H), 4,13 (a, 2H), 2,83 (t, J = 7,4 Hz, 2H), 2,77 (t, J = 7,4 Hz, 2H), 2,32 (s, 3H), 2,08 (s, 3H), 2,05-1,90 (m, 2H), 1,65 (s, 3H). TLC: Fr 0.54 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.80-7.70 (m, 2H), 7.37 (d, J = 7.8 Hz, 1H), 7.05 (s, 1H), 6.99 (s, 1H), 6.87 (d, J = 3.3 Hz, 1H), 30 6.17 (d, J = 3.3 Hz, 1H), 4.99 (a, 2H), 4.72 (s , 2H), 4.13 (a, 2H), 2.83 (t, J = 7.4 Hz, 2H), 2.77 (t, J = 7.4 Hz, 2H), 2.32 (s , 3H), 2.08 (s, 3H), 2.05-1.90 (m, 2H), 1.65 (s, 3H).

Ejemplo 5(3) Ácido 4-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]-3-metilbenzoico Example 5 (3) 4- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsofonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid

5 TLC: Fr 0,54 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,77 (s, 1H), 7,74 (d, J = 8,1 Hz, 1H), 7,38 (d, 3 = 8,1 Hz, 1H), 7,09 (s, 1H), 7,02 (s, 1H), 6,85 (d, J = 3,3 Hz, 1H), 6,20-6,15 (m, 1H), 5,01 (a, 2H), 3,41 (a, 2H), 2,86 (t, J = 7,4 Hz, 2H), 2,79 (t, J = 7,4 Hz, 2H), 2,32 (s, 3H), 2,10 (s, 3H), 2,10-1,95 (m, 2H), 0,90-0,70 (m, 1H), 0,35-0,25 (m, 2H), 0,05-(-0,05) (m, 2H). 5 TLC: Fr 0.54 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.77 (s, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.38 (d, 3 = 8.1 Hz, 1H), 7 , 09 (s, 1H), 7.02 (s, 1H), 6.85 (d, J = 3.3 Hz, 1H), 6.20-6.15 (m, 1H), 5.01 ( a, 2H), 3.41 (a, 2H), 2.86 (t, J = 7.4 Hz, 2H), 2.79 (t, J = 7.4 Hz, 2H), 2.32 ( s, 3H), 2.10 (s, 3H), 2.10-1.95 (m, 2H), 0.90-0.70 (m, 1H), 0.35-0.25 (m, 2H), 0.05 - (- 0.05) (m, 2H).

10 Ejemplo 5(4)Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico Example 5 (4) 4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid

15 TLC: Fr 0,55 (acetato de etilo : metanol = 9:1); RMN: δ 8,14 (d, J = 8,4 Hz, 2H), 7,85 (s, 1H), 7,78 (d, J = 8,1 Hz, 1H), 7,70 (d, J = 8,1 Hz, 1H), 7,51-7,37 (m, 4H), 7,18 (s, 1H), 6,93 (s, 1H), 5,17 y 4,96 (cada m a, total 2H), 3,85-3,62 (m a, 2H), 2,34 (s, 3H), 1,82-1,69 (m, 1H), 0,97 (s a, 6H). TLC: Fr 0.55 (ethyl acetate: methanol = 9: 1); NMR: δ 8.14 (d, J = 8.4 Hz, 2H), 7.85 (s, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.51-7.37 (m, 4H), 7.18 (s, 1H), 6.93 (s, 1H), 5.17 and 4.96 (each ma, total 2H), 3.85-3.62 (ma, 2H), 2.34 (s, 3H), 1.82-1.69 (m, 1H), 0.97 (sa, 6H).

20 Ejemplo 5(5)Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico Example 5 (5) 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid

25 TLC: Fr 0,55 (acetato de etilo:metanol = 9:1); RMN: δ 8,15 (d, J = 8,4 Hz, 2H), 7,72 (d, J = 9,0 Hz, 2H), 7,61 (s, 1H), 7,60 (d, J = 9,0 Hz, 2H), 7,51-7,46 (m, 1H), 7,44-7,3 (m, 1H), 7,24 (s, 1H), 7,03 (s, 1H), 5,24 (s, 2H), 4,84-4,75 (m, 1H), 2,52 (s, 3H), 1,26 (d, J = 6,6 Hz, 3H), 1,17 (d, J = 6,6 Hz, 3H). 25 TLC: Fr 0.55 (ethyl acetate: methanol = 9: 1); NMR: δ 8.15 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 9.0 Hz, 2H), 7.61 (s, 1H), 7.60 (d, J = 9.0 Hz, 2H), 7.51-7.46 (m, 1H), 7.44-7.3 (m, 1H), 7.24 (s, 1H), 7.03 (s , 1H), 5.24 (s, 2H), 4.84-4.75 (m, 1H), 2.52 (s, 3H), 1.26 (d, J = 6.6 Hz, 3H) , 1.17 (d, J = 6.6 Hz, 3H).

Ejemplo 5(6) Ácido 4-[3-N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (6) 4- [3-N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

5 TLC: Fr 0,63 (acetato de etilo:metanol = 9:1); RMN: δ 7,98-7,96 (m, 2H), 7,84 (s, 1H), 7,78 (d, J = 8,1 Hz, 1H), 7,72 (d, J = 8,1 Hz, 1H), 7,52-7,47 (m, 1H), 7,427,37 (m, 2H), 7,21 (s, 1H), 6,95 (s, 1H), 5,10 y 4,96 (cada m a, total 2H), 3,84-3,60 (m a, 2H), 2,41 (s, 3H), 2,34 (s, 3H), 1,82-1,68 (m, 1H), 0,96 (s a, 6H). 5 TLC: Rf 0.63 (ethyl acetate: methanol = 9: 1); NMR: δ 7.98-7.96 (m, 2H), 7.84 (s, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8 , 1 Hz, 1H), 7.52-7.47 (m, 1H), 7.427.37 (m, 2H), 7.21 (s, 1H), 6.95 (s, 1H), 5.10 and 4.96 (each ma, total 2H), 3.84-3.60 (ma, 2H), 2.41 (s, 3H), 2.34 (s, 3H), 1.82-1.68 (m, 1H), 0.96 (sa, 6H).

10 Ejemplo 5(7)Ácido 4-[3-[N-isopropil-N-[2-(4-metiltiazolil)sulfonil]amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (7) 4- [3- [N-Isopropyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

15 TLC: Fr 0,56 (acetato de etilo : metanol =9:1); RMN: δ 8,00-7,97 (m, 2H), 7,76-7,65 (m, 3H), 7,61 (s, 1H), 7,52-7,47 (m, 1H), 7,40-7, 3 5 (m, 1H), 7,26 (s, 1H), 7,04 (s, 1H), 5,22 (d, J = 15,0 Hz, 1H), 5,17 (d, J = 15,0 Hz, 1H), 4,83-4,73 (m, 1H), 2,53 (s, 3H), 2,46 (s, 3H), 1,25 (d, J = 6,6 Hz, 3H), 1,16 (d, J = 6,6 Hz, 3H). TLC: Fr 0.56 (ethyl acetate: methanol = 9: 1); NMR: δ 8.00-7.97 (m, 2H), 7.76-7.65 (m, 3H), 7.61 (s, 1H), 7.52-7.47 (m, 1H) , 7.40-7, 3 5 (m, 1H), 7.26 (s, 1H), 7.04 (s, 1H), 5.22 (d, J = 15.0 Hz, 1H), 5 , 17 (d, J = 15.0 Hz, 1H), 4.83-4.73 (m, 1H), 2.53 (s, 3H), 2.46 (s, 3H), 1.25 ( d, J = 6.6 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H).

20 Ejemplo 5(8)Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico Example 5 (8) 4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid

25 TLC: Fr 0,67 (acetato de etilo:metanol = 9:1); RMN: δ 7,84-7,69 (m, 4H), 7,58 (d, J = 8,1 Hz, 2H), 7,51 -7,45 (m, 1H), 7,41 -7,35 (m, 3H), 7,18 (s, 1H), 6,93 (s, 1H), 6,49 (d, J = 16,2 Hz, 1H), 5,02 y 4,91 (cada m a, total 2H), 3,84-3,62 (m a, 2H), 2,33 (s, 3H), 1,82-1,68 (m, 1H), 0,91 (s a, 6H). TLC: Fr 0.67 (ethyl acetate: methanol = 9: 1); NMR: δ 7.84-7.69 (m, 4H), 7.58 (d, J = 8.1 Hz, 2H), 7.51-7.45 (m, 1H), 7.41-7 , 35 (m, 3H), 7.18 (s, 1H), 6.93 (s, 1H), 6.49 (d, J = 16.2 Hz, 1H), 5.02 and 4.91 ( each ma, total 2H), 3.84-3.62 (ma, 2H), 2.33 (s, 3H), 1.82-1.68 (m, 1H), 0.91 (sa, 6H) .

Ejemplo 5(9) Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico Example 5 (9) 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid

5 TLC: Fr 0,61 (acetato de etilo : metanol = 9:1); RMN: δ 7,80 (d, J = 16,9 Hz, 1H), 7,71 (d, J = 8,7 Hz, 2H), 7,61 -7,46 (m, 6H), 7,39-7,34 (m, 1H), 7,24 (s, 1H), 7,03 (s, 1H), 6,48 (d, J = 16,9 Hz, 1H), 5,19 (s, 2H), 4,85-4,72 (m, 1H), 2,51 (s, 3H), 1,25 (d, J = 6,6 Hz, 3H), 1,16 (d, J = 6,6 Hz, 3H). 5 TLC: Rf 0.61 (ethyl acetate: methanol = 9: 1); NMR: δ 7.80 (d, J = 16.9 Hz, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.61-7.46 (m, 6H), 7, 39-7.34 (m, 1H), 7.24 (s, 1H), 7.03 (s, 1H), 6.48 (d, J = 16.9 Hz, 1H), 5.19 (s , 2H), 4.85-4.72 (m, 1H), 2.51 (s, 3H), 1.25 (d, J = 6.6 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H).

10 Ejemplo 5(11)Ácido 4-[6-[N-etil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico Example 5 (11) 4- [6- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid

15 TLC: Fr 0,59 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,77 (s, 1H), 7,74 (d, J = 7,8 Hz, 1H), 7,3 8 (d, J = 7,8 Hz, 1 H), 7,10 (s, 1H), 6,95 (s, 1H), 6,86 (d, J = 3,3 Hz, 1H), 6,16 (d, J = 3,3 Hz, 1H), 5,01 (a, 2H), 3,58 (a, 2H), 2,86 (t, J = 7,4 Hz, 2H), 2,79 (t, J = 7,4 Hz, 2H), 2,32 (s, 3H), 2,10 (s, 3H), 2,10-1,95 (m, 2H), 0,99 (t, J = 7,2 Hz, 3H). TLC: Fr 0.59 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.77 (s, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.3 8 (d, J = 7.8 Hz, 1 H) , 7.10 (s, 1H), 6.95 (s, 1H), 6.86 (d, J = 3.3 Hz, 1H), 6.16 (d, J = 3.3 Hz, 1H) , 5.01 (a, 2H), 3.58 (a, 2H), 2.86 (t, J = 7.4 Hz, 2H), 2.79 (t, J = 7.4 Hz, 2H) , 2.32 (s, 3H), 2.10 (s, 3H), 2.10-1.95 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H).

20 Ejemplo 5(13)Ácido 4-[6-[N-etil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 5 (13) 4- [6- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

25 TLC: Fr 0,53 (cloroformo:metanol =9:1); RMN: δ 7,77 (d, J = 16,2 Hz, 1H), 7,55 (d, J = 8,4 Hz, 2H), 7,37 (d, J = 8,4 Hz, 2H), 7,08 (s, 1H), 6,80 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 6,47 (d, J = 16,2 Hz, 1H), 5,94 (d, J = 3,3 Hz, 1H), 4,97 (s, 2 H), 3,82-3,65 (m, 2H), 2,90-2,80 (m, 4H), 2,15 (s, 3H), 2,08 (quint, J = 7,2 Hz, 2H), 1,14 (t, J = 7,2 Hz, 3H). 25 TLC: Fr 0.53 (chloroform: methanol = 9: 1); NMR: δ 7.77 (d, J = 16.2 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H) , 7.08 (s, 1H), 6.80 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.47 (d, J = 16.2 Hz, 1H) , 5.94 (d, J = 3.3 Hz, 1H), 4.97 (s, 2 H), 3.82-3.65 (m, 2H), 2.90-2.80 (m, 4H), 2.15 (s, 3H), 2.08 (quint, J = 7.2 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H).

30 Ejemplo 5(14)Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-propilamino]indan-5-iloximetil]cinámico Example 5 (14) 4- [6- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,54 (cloroformo:metanol = 9:1); RMN: δ 7,78 (d, J = 15,9 Hz, 1H), 7,55 (d, J = 8,1 Hz, 2H), 7,37 (d, J = 8,1 Hz, 2H), 7,08 (s, 1H), 6,79 (s, 1H), 6,74 (d, J = 3,3 Hz, 1H), 6,46 (d, J = 15,9 Hz, 1H), 5,94 (d a, J = 3,3 Hz, 1H), 4,97 (s a, 2H), 3,65-3 .61 (m, 2H), 2,90-2,80 (m, 4H), 2,15 (s, 3H), 2,08 (quint, J = 7,5 Hz, 2H), 1,53 (sext, J = 7,2 Hz, 2H), 0,89 (t, J = 7,2 Hz, 3H). TLC: Fr 0.54 (chloroform: methanol = 9: 1); NMR: δ 7.78 (d, J = 15.9 Hz, 1H), 7.55 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H) , 7.08 (s, 1H), 6.79 (s, 1H), 6.74 (d, J = 3.3 Hz, 1H), 6.46 (d, J = 15.9 Hz, 1H) , 5.94 (da, J = 3.3 Hz, 1H), 4.97 (sa, 2H), 3.65-3 .61 (m, 2H), 2.90-2.80 (m, 4H ), 2.15 (s, 3H), 2.08 (quint, J = 7.5 Hz, 2H), 1.53 (sext, J = 7.2 Hz, 2H), 0.89 (t, J = 7.2 Hz, 3H).

Ejemplo 5(15) Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]fenoximetil]-3-metilbenzoico Example 5 (15) 4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] phenoxymethyl] -3-methylbenzoic acid

10 TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,00-7,93 (m, 2H), 7,44 (d, J = 8,1 Hz, 1H), 7,02 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 6,69 (s, 1H), 5,96 (m, 1H), 4,94 (s, 2H), 4,77 (s, 2H), 4,27 (s, 2H), 2,38 (s, 3H), 2,22 (s, 3H), 2,18 (s, 3H), 2,12 (s, 3H), 1,78 (s, 3H). 10 TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.00-7.93 (m, 2H), 7.44 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.75 (d, J = 3 , 3 Hz, 1H), 6.69 (s, 1H), 5.96 (m, 1H), 4.94 (s, 2H), 4.77 (s, 2H), 4.27 (s, 2H ), 2.38 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 1.78 (s, 3H).

Ejemplo 5(16)15 Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]indan-5-iloximetil]cinámico Example 5 (16) 15 4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,61 (cloroformo:metanol = 9:1); TLC: Fr 0.61 (chloroform: methanol = 9: 1);

20 RMN: δ 7,78 (d, J = 15,9 Hz, 1H), 7,56 (d, J = 8,4 Hz, 2H), 7,36 (d, J = 8,4 Hz, 2H), 7,09 (s, 1H), 6,76 (s, 1H), 6,74 (d, J = 3,0 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,94 (d, J = 3,0 Hz, 1H), 4,95 (s a, 2H), 4,77 (s, 2H), 4,38-4,18 (m, 2H), 2,90-2,75 (m, 4H), 2,14 (s, 3H), 2,07 (quint, J = 7,5 Hz, 2H), 1,78 (s, 3H). NMR: δ 7.78 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H ), 7.09 (s, 1H), 6.76 (s, 1H), 6.74 (d, J = 3.0 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H ), 5.94 (d, J = 3.0 Hz, 1H), 4.95 (sa, 2H), 4.77 (s, 2H), 4.38-4.18 (m, 2H), 2 , 90-2.75 (m, 4H), 2.14 (s, 3H), 2.07 (quint, J = 7.5 Hz, 2H), 1.78 (s, 3H).

Ejemplo 5(17)25 Ácido 4-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 5 (17) 25 4- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,51 (cloroformo:metanol = 9:1); TLC: Fr 0.51 (chloroform: methanol = 9: 1);

30 RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,55 (d, J = 8,4 Hz, 2H), 7,38 (d, J = 8,4 Hz, 2H), 7,15 (s, 1H), 6,79 (s, 1H), 6,74 (d, J = 3,3 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,94 (d, J = 3,3 Hz, 1H), 4,97 (s a, 2H), 3,65-3,50 (m, 2H), 2,92-2,70 (m, 4H), 2,15 (s, 3H), 2,08 (quint, J = 7,5 Hz, 2H), 1,00-0,85 (m, 1H), 0,45-0,36 (m, 2H), 0,20-0,05 (m, 2H). 30 NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H ), 7.15 (s, 1H), 6.79 (s, 1H), 6.74 (d, J = 3.3 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H ), 5.94 (d, J = 3.3 Hz, 1H), 4.97 (sa, 2H), 3.65-3.50 (m, 2H), 2.92-2.70 (m, 4H), 2.15 (s, 3H), 2.08 (quint, J = 7.5 Hz, 2H), 1.00-0.85 (m, 1H), 0.45-0.36 (m , 2H), 0.20-0.05 (m, 2H).

Ejemplo 5(18) Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]cinámico Example 5 (18) 4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid

5 TLC: Fr 0,57 (cloroformo:metanol =9:1); RMN: δ 7,79 (d, J = 15,9 Hz, 1H), 7,56 (d, J = 8,4 Hz, 2H), 7,38 (d, J = 8,4 Hz, 2H), 7,07 (s, 1H), 6,78 (s, 1H), 6,76 (d, J = 3,3 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,96 (d, J = 3,3 Hz, 1H), 5,96-5,77 (m, 1H), 5,13-5,03 (m, 2H), 4,97 (s, 2H), 4,42-4,20 (m, 2H), 2,90-2,80 (m, 4H), 2,16 (s, 3H), 2,07 (quint, J = 7,5 Hz, 2H). 5 TLC: Fr 0.57 (chloroform: methanol = 9: 1); NMR: δ 7.79 (d, J = 15.9 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H) , 7.07 (s, 1H), 6.78 (s, 1H), 6.76 (d, J = 3.3 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H) , 5.96 (d, J = 3.3 Hz, 1H), 5.96-5.77 (m, 1H), 5.13-5.03 (m, 2H), 4.97 (s, 2H ), 4.42-4.20 (m, 2H), 2.90-2.80 (m, 4H), 2.16 (s, 3H), 2.07 (quint, J = 7.5 Hz, 2H).

10 Ejemplo 5(19)Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-propilamino]indan-5-iloximetil]benzoico Example 5 (19) 3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid

15 TLC: Fr 0,40 (cloroformo:metanol = 10:1); RMN: δ 7,95 (d, J = 7,8 Hz, 1H), 7,93 (s, 1H), 7,46 (d, J = 7,8 Hz, 1H), 7,10 (s, 1H), 6,81 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 5,95 (dd, J = 3,3, 0,9 Hz, 1H), 4,96 (s, 2H), 3,76-3,47 (m, 2H), 2,92-2,82 (m, 4H), 2,37 (s, 3H), 2,13 (s, 3H), 2,15-2,03 (m, 2H), 1,60-1,47 (m, 2H), 0,89 (t, J = 7,5 Hz, 3H). TLC: Fr 0.40 (chloroform: methanol = 10: 1); NMR: δ 7.95 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.10 (s, 1H), 6.81 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 5.95 (dd, J = 3.3, 0.9 Hz, 1H), 4, 96 (s, 2H), 3.76-3.47 (m, 2H), 2.92-2.82 (m, 4H), 2.37 (s, 3H), 2.13 (s, 3H) , 2.15-2.03 (m, 2H), 1.60-1.47 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H).

20 Ejemplo 5(20)Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]benzoico Example 5 (20) 3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid

25 TLC: Fr 0,41 (cloroformo:metanol = 10:1); RMN: δ 7,95 (d, J = 7,8 Hz, 1H), 7,94 (s, 1H), 7,47 (d, J = 7,8 Hz, 1H), 7,08 (s, 1H), 6,80 (s, 1H), 6,78 (d, J = 3,3 Hz, 1H), 5,97 (d, J = 3,3 Hz, 1H), 5,85 (m, 1H), 5,10 (dd, J = 16,8, 1,2 Hz, 1H), 5,05 (dd, J = 9,9, 1,2 Hz, 1H), 4,97 (s, 2H), 4,43-4,18 (m, 2H), 2,91-2,81 (m, 4H), 2,37 (s, 3H), 2,15 (s, 3H), 2,13-2,03 (m, 2H). 25 TLC: Fr 0.41 (chloroform: methanol = 10: 1); NMR: δ 7.95 (d, J = 7.8 Hz, 1H), 7.94 (s, 1H), 7.47 (d, J = 7.8 Hz, 1H), 7.08 (s, 1H), 6.80 (s, 1H), 6.78 (d, J = 3.3 Hz, 1H), 5.97 (d, J = 3.3 Hz, 1H), 5.85 (m, 1H), 5.10 (dd, J = 16.8, 1.2 Hz, 1H), 5.05 (dd, J = 9.9, 1.2 Hz, 1H), 4.97 (s, 2H ), 4.43-4.18 (m, 2H), 2.91-2.81 (m, 4H), 2.37 (s, 3H), 2.15 (s, 3H), 2.13- 2.03 (m, 2H).

30 Ejemplo 5(22)Ácido 4-[4,5-dimetil-2-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico Example 5 (22) 4- [4,5-dimethyl-2- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid

TLC: Fr 0,49 (diclorometano:metanol = 10:1); RMN: δ 7,96-7,90 (m, 2H), 7,32 (d, J = 8,1 Hz, 1H), 7,06 (s, 1H), 6,90 (m, 1H), 6,74 (s, 1H), 4,87 (s a, 2H), 3,85 (a, 5 2H), 2,34 (s, 3H), 2,32 (d, J = 0,9 Hz, 3H), 2,25 (s, 3H), 2,19 (s, 3H), 1,18 (t, J = 7,2 Hz, 3H). TLC: Fr 0.49 (dichloromethane: methanol = 10: 1); NMR: δ 7.96-7.90 (m, 2H), 7.32 (d, J = 8.1 Hz, 1H), 7.06 (s, 1H), 6.90 (m, 1H), 6.74 (s, 1H), 4.87 (sa, 2H), 3.85 (a, 5 2H), 2.34 (s, 3H), 2.32 (d, J = 0.9 Hz, 3H), 2.25 (s, 3H), 2.19 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H).

Ejemplo 5(23)Example 5 (23)

Ácido 4-[4,5-dimetil-2-[N-(4-metil-2-tiazolilsulfonil)-N-propilamino]fenoximetil]-3-metilbenzoico 4- [4,5-dimethyl-2- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] phenoxymethyl] -3-methylbenzoic acid

TLC: Fr 0,49 (diclorometano:metanol = 10:1); TLC: Fr 0.49 (dichloromethane: methanol = 10: 1);

RMN (DMSOd6): δ 12,88 (s, 1H), 7,78-7,72 (m, 2H), 7,49 (m, 1H), 7,25 (d, J = 7,8 Hz, 1H), 7,03 (s, 1H), 6,95 (s, 1H), NMR (DMSOd6): δ 12.88 (s, 1H), 7.78-7.72 (m, 2H), 7.49 (m, 1H), 7.25 (d, J = 7.8 Hz, 1H), 7.03 (s, 1H), 6.95 (s, 1H),

4,88 (a, 2H), 3,59 (a, 2H), 2,28 (s, 3H), 2,22 (s, 3H), 2,18 (s, 3H), 2,13 (s, 3H), 1,44-1,35 (m, 2H), 0,81 (t, J = 7,2 Hz, 15 3H). 4.88 (a, 2H), 3.59 (a, 2H), 2.28 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 2.13 (s , 3H), 1.44-1.35 (m, 2H), 0.81 (t, J = 7.2 Hz, 15H).

Ejemplo 5(24)Example 5 (24)

Ácido 4-[4,5-dimetil-2-[N-(4-metil-2-tiazolilsulfonil)-N-(2-propenil)amino]fenoximetil]-3-metilbenzoico 4- [4,5-dimethyl-2- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] -3-methylbenzoic acid

RMN (DMSOd6): δ 12,88 (s, 1H), 7,78-7,72 (m, 2H), 7,50 (s, 1H), 7,26 (d, J = 7,5 Hz, 1H), 7,01 (s, 1H), 6,95 (s, 1H), NMR (DMSOd6): δ 12.88 (s, 1H), 7.78-7.72 (m, 2H), 7.50 (s, 1H), 7.26 (d, J = 7.5 Hz, 1H), 7.01 (s, 1H), 6.95 (s, 1H),

5,74 (m, 1H), 5,09 (d, J = 17,1 Hz, 1H), 5,04 (d, J = 9,9 Hz, 1H), 4,89 (a, 2H), 4,27 (a, 2H), 2,29 (s, 3H), 2,21 (s, 3H), 25 2,18 (s, 3H), 2,12 (s, 3H). 5.74 (m, 1H), 5.09 (d, J = 17.1 Hz, 1H), 5.04 (d, J = 9.9 Hz, 1H), 4.89 (a, 2H), 4.27 (a, 2H), 2.29 (s, 3H), 2.21 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H).

Ejemplo 5(25) Ácido 4-[2-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino-4,5-dimetil]fenoximetil]-3-metilbenzoico Example 5 (25) 4- [2- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino-4,5-dimethyl] phenoxymethyl] -3-methylbenzoic acid

TLC: Fr 0,49 (diclorometano:metanol = 10:1); RMN (DMSO-d6): δ 12,87 (a, 1H), 7,78-7,72 (m, 2H), 7,48 (s, 1H), 7,25 (d, J = 7,5 Hz, 1H), 7,03 (s, 1H), 7,00 (s, 1H), TLC: Fr 0.49 (dichloromethane: methanol = 10: 1); NMR (DMSO-d6): δ 12.87 (a, 1H), 7.78-7.72 (m, 2H), 7.48 (s, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.03 (s, 1H), 7.00 (s, 1H),

4,90 (a, 2H), 3,45 (a, 2H), 2,27 (s, 3H), 2,23 (s, 3H), 2,17 (s, 3H), 2,14 (s, 3H), 0,82 (m, 1H), 0,38-0,30 (m, 2H), 0,100,02 (m, 2H). 4.90 (a, 2H), 3.45 (a, 2H), 2.27 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 2.14 (s , 3H), 0.82 (m, 1H), 0.38-0.30 (m, 2H), 0.100.02 (m, 2H).

Ejemplo 5(26) Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico Example 5 (26) 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid

10 RMN: δ 7,99-7,94 (m, 2H), 7,47 (d, J = 8,1 Hz, 1H), 7,04 (m, 1H), 6,79 (s, 1H), 6,77 (s, 1H), 5,06 (d, J = 12,3 Hz, 1H), 4,95 (d, J = 12,3 Hz, 1H), 3,95 (d, J = 15,3 Hz, 1H), 3,73 (d, J = 15,3 Hz, 1H), 2,420 (s, 3H), 2,417 (s, 3H), 2,23 (s, 3H), 2,11 (s, 3H), 1,25 (s, 3H), 1,21 (s, 3H). 10 NMR: δ 7.99-7.94 (m, 2H), 7.47 (d, J = 8.1 Hz, 1H), 7.04 (m, 1H), 6.79 (s, 1H) , 6.77 (s, 1H), 5.06 (d, J = 12.3 Hz, 1H), 4.95 (d, J = 12.3 Hz, 1H), 3.95 (d, J = 15.3 Hz, 1H), 3.73 (d, J = 15.3 Hz, 1H), 2,420 (s, 3H), 2,417 (s, 3H), 2.23 (s, 3H), 2.11 (s, 3H), 1.25 (s, 3H), 1.21 (s, 3H).

Ejemplo 5(28)15 Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]benzoico Example 5 (28) 4- [4,5-Dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] benzoic acid

TLC: Fr 0,41 (cloroformo:metanol = 9:1); 20 RMN: δ 8,10 (d, J = 8,4 Hz, 2H), 7,43 (d, J = 8,4 Hz, 2H), 7,01 (s, 1H), 6,76 (d, J = 3,3 Hz, 1H), 6,71 (s, 1H), 5,965,93 (m, 1H), 5,02 (s, 2H), 3,83-3,65 (m, 2H), 2,23 (s, 3H), 2,18 (s, 3H), 2,14 (s, 3H), 1,14 (t, J = 7,2 Hz, 3H). TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR: δ 8.10 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.01 (s, 1H), 6.76 (d , J = 3.3 Hz, 1H), 6.71 (s, 1H), 5.965.93 (m, 1H), 5.02 (s, 2H), 3.83-3.65 (m, 2H) , 2.23 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H).

Ejemplo 5(29)Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-propilamino]fenoximetil]benzoico 25 Example 5 (29) 4- [4,5-dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] phenoxymethyl] benzoic acid

TLC: Fr 0,43 (cloroformo:metanol = 9:1); TLC: Fr 0.43 (chloroform: methanol = 9: 1);

RMN: δ 8,11 (d, J = 8,4 Hz, 2H), 7,43 (d, J = 8,4 Hz, 2H), 7,02 (s, 1H), 6,74 (d, J = 3,0 Hz, 1H), 6,70 (s, 1H), 5,9630 5,93 (m, 1H), 5,01 (s, 2H), 3,75-3,53 (m, 2H), 2,22 (s, 3H), 2,18 (s, 3H), 2,14 (s, 3H), 1,60-1,46 (m, 2H), 0,90 (t, J = NMR: δ 8.11 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.02 (s, 1H), 6.74 (d, J = 3.0 Hz, 1H), 6.70 (s, 1H), 5.9630 5.93 (m, 1H), 5.01 (s, 2H), 3.75-3.53 (m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H), 1.60-1.46 (m, 2H), 0.90 (t, J =

7,2 Hz, 3H). 7.2 Hz, 3H).

Ejemplo 5(30)Example 5 (30)

Ácido 4-[6-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico 35 4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid 35

TLC: Fr 0,36 (diclorometano: metanol = 19:1); RMN: δ 8,11 (d, J = 8,7 Hz, 2H), 7,35 (d, J = 8,7 Hz, 2H), 7,14 (s, 1H), 6,92 (s a, 1H), 6,74 (s, 1H), 5,10-4,70 (s a, 5 2H), 4,80 (s a, 2H), 4,60-4,20 (s a, 2H), 2,88-2,82 (m, 4H), 2,32 (d, J = 0,9 Hz, 3H), 2,07 (m, 2H), 1,83 (s, 3H). TLC: Fr 0.36 (dichloromethane: methanol = 19: 1); NMR: δ 8.11 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.14 (s, 1H), 6.92 (s, 1H), 6.74 (s, 1H), 5.10-4.70 (sa, 5 2H), 4.80 (sa, 2H), 4.60-4.20 (sa, 2H), 2, 88-2.82 (m, 4H), 2.32 (d, J = 0.9 Hz, 3H), 2.07 (m, 2H), 1.83 (s, 3H).

Ejemplo 5(31)Example 5 (31)

Ácido 4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]benzoico 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid

RMN: δ 8,11 (d, J = 8,7 Hz, 2H), 7,35 (d, J = 8,7 Hz, 2H), 7,13 (s, 1H), 6,93 (s a, 1H), 6,76 (s, 1H), 5,89 (ddt, J = NMR: δ 8.11 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.13 (s, 1H), 6.93 (s, 1H), 6.76 (s, 1H), 5.89 (ddt, J =

17,1, 10,2, 6,3 Hz, 1H), 5,17-5,06 (m, 2H), 4,92 (s a, 2H), 4,70-4,10 (s a, 2H), 2,89-2,83 (m, 4H), 2,34 (d, J = 0,9 Hz, 15 3H), 2,08 (m, 2H). 17.1, 10.2, 6.3 Hz, 1H), 5.17-5.06 (m, 2H), 4.92 (sa, 2H), 4.70-4.10 (sa, 2H) , 2.89-2.83 (m, 4H), 2.34 (d, J = 0.9 Hz, 15 3H), 2.08 (m, 2H).

Ejemplo 5(32)Example 5 (32)

Ácido 4-[6-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

TLC: Fr 0,36 (diclorometano:metanol = 19:1); TLC: Fr 0.36 (dichloromethane: methanol = 19: 1);

RMN: δ 8,10 (d, J = 8,7 Hz, 2H), 7,35 (d, J = 8,7 Hz, 2H), 7,22 (s, 1H), 6,89 (s a, 1H), 6,78 (s, 1H), 5,10-4,70 (m, 2H), NMR: δ 8.10 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.22 (s, 1H), 6.89 (s, 1H), 6.78 (s, 1H), 5.10-4.70 (m, 2H),

3,90-3,50 (m, 2H), 2,90-2,85 (m, 4H), 2,32 (d, J = 0,9 Hz, 3H), 2,09 (m, 2H), 1,00 (m, 1H), 0,43 (m, 2H), 0,20 (s a, 25 2H). 3.90-3.50 (m, 2H), 2.90-2.85 (m, 4H), 2.32 (d, J = 0.9 Hz, 3H), 2.09 (m, 2H) , 1.00 (m, 1H), 0.43 (m, 2H), 0.20 (sa, 25 2H).

Ejemplo 5(33) Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (33) 4- [3- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

TLC: Fr 0,52 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,92-7,80 (m, 3H), 7,77 (d, J = 8,1 Hz, 1H), 7,69 (d, J = 8,1 Hz, 1H), 7,63 (s, 1H), 7,60 (s, 1H), TLC: Fr 0.52 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.92-7.80 (m, 3H), 7.77 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H) , 7.63 (s, 1H), 7.60 (s, 1H),

7,57-7,50 (m, 1H), 7,45-7,36 (m, 1H), 6,95 (d, J = 3,3 Hz, 1H), 6,29 (d, J = 3,3 Hz, 1H), 5,26 y 5,24 (cada d, J = 13,5 Hz, cada 1H), 4,34 (sept, J = 6,6 Hz, 1H), 2,42 (s, 3H), 2,34 (s, 3H), 1,06 y 1,00 (cada d, J = 6,6 Hz, cada 3H). 7.57-7.50 (m, 1H), 7.45-7.36 (m, 1H), 6.95 (d, J = 3.3 Hz, 1H), 6.29 (d, J = 3.3 Hz, 1H), 5.26 and 5.24 (every d, J = 13.5 Hz, every 1H), 4.34 (Sept, J = 6.6 Hz, 1H), 2.42 ( s, 3H), 2.34 (s, 3H), 1.06 and 1.00 (every d, J = 6.6 Hz, every 3H).

Ejemplo 5(34) Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (34) 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

TLC: Fr 0,50 (cloroformo:metanol = 9:1); TLC: Fr 0.50 (chloroform: methanol = 9: 1);

10 RMN (DMSOd6): δ 7,88 (d, J = 7,8 Hz, 1H), 7,86-7,74 (m, 4H), 7,59 (s, 1H), 7,56-7,36 (m, 3H), 6,86 (d, J = 3,3 Hz, 1H), 6,19 (d, J = 3,3 Hz, 1H), 5,40-4,90 (a, 2H), 3,47 (d a, J = 6,9 Hz, 2H), 2,39 (s, 3H), 2,12 (s, 3H), 1,65-1,50 (m, 1H), 0,83 (d a, J = 6,3 Hz, 6H). 10 NMR (DMSOd6): δ 7.88 (d, J = 7.8 Hz, 1H), 7.86-7.74 (m, 4H), 7.59 (s, 1H), 7.56-7 , 36 (m, 3H), 6.86 (d, J = 3.3 Hz, 1H), 6.19 (d, J = 3.3 Hz, 1H), 5.40-4.90 (a, 2H), 3.47 (da, J = 6.9 Hz, 2H), 2.39 (s, 3H), 2.12 (s, 3H), 1.65-1.50 (m, 1H), 0.83 (da, J = 6.3 Hz, 6H).

Ejemplo 5(35)15 Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico Example 5 (35) 15 4- [3- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid

20 RMN (DMSOd6): δ 7,87 (d, J = 7,8 Hz, 1H), 7,82 (d, J = 7,8 Hz, 1H), 7,73 (d, J = 8,4 Hz, 2H), 7,67-7,46 (m, 6H), 7,447,34 (m, 1H), 6,94 (d, J = 3,3 Hz, 1H), 6,56 (d, J = 15,9 Hz, 1H), 6,28 (d, J = 3,3 Hz, 1H), 5,27 y 5,21 (cada d, J = 13,2 Hz, cada 1H), 4,36 (sept, J = 6,6 Hz, 1H), 2,33 (s, 3H), 1,08 y 1,03 (cada d, J = 6,6 Hz, cada 3H). NMR (DMSOd6): δ 7.87 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.67-7.46 (m, 6H), 7.447.34 (m, 1H), 6.94 (d, J = 3.3 Hz, 1H), 6.56 (d, J = 15.9 Hz, 1H), 6.28 (d, J = 3.3 Hz, 1H), 5.27 and 5.21 (each d, J = 13.2 Hz, each 1H), 4.36 (sept, J = 6.6 Hz, 1H), 2.33 (s, 3H), 1.08 and 1.03 (every d, J = 6.6 Hz, every 3H).

Ejemplo 5(36)25 Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico Example 5 (36) 25 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid

30 RMN (DMSOd6): δ 7,88 (d, J = 8,4 Hz, 1H), 7,81 (s, 1H), 7,80 (d, J = 8,1 Hz, 1H), 7,72 (d, J = 7,8 Hz, 2H), 7,61 (d, J = 15,9 Hz, 1H), 7,55-7,34 (m, 2H), 7,50 (s, 1H), 7,44 (d, J = 7,8 Hz, 2H), 6,82 (d, J = 3,6 Hz, 1H), 6,56 (d, J = 15,9 Hz, 1H), 6,16 (d, J = 3,6 Hz, 1H), 5,40-4,90 (a, 2H), 3,49 (d, J = 6,6 Hz, 2H), 2,13 (s, 3H), 1,64-1,48 (m, 1H), 0,85 (d, J = 6,6 Hz, 6H). NMR (DMSOd6): δ 7.88 (d, J = 8.4 Hz, 1H), 7.81 (s, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7, 72 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 15.9 Hz, 1H), 7.55-7.34 (m, 2H), 7.50 (s, 1H ), 7.44 (d, J = 7.8 Hz, 2H), 6.82 (d, J = 3.6 Hz, 1H), 6.56 (d, J = 15.9 Hz, 1H), 6.16 (d, J = 3.6 Hz, 1H), 5.40-4.90 (a, 2H), 3.49 (d, J = 6.6 Hz, 2H), 2.13 (s , 3H), 1.64-1.48 (m, 1H), 0.85 (d, J = 6.6 Hz, 6H).

Ejemplo 5(37) Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilciámico Example 5 (37) 4- [3- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylcylamic acid

5 TLC: Fr 0,46 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,87 (d, J = 8,1 Hz, 1H), 7,86 (d, J = 8,4 Hz, 1H), 7,64-7,48 (m, 7H), 7,44-7,36 (m, 1H), 6,93 (d, J = 3,6 Hz, 1H), 6,54 (d, J = 15,9 Hz, 1H), 6,29 (d, J = 3,6 Hz, 1H), 5,23 y 5,18 (cada d, J = 14,4 Hz, cada 1H), 4,33 (sept, J = 6,6 Hz, 1H), 2,39 (s, 3H), 2,34 (s, 3H), 1,06 y 1,00 (cada d, J = 6,6 Hz, cada 3H). 5 TLC: Fr 0.46 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.87 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.64-7.48 (m, 7H) , 7.44-7.36 (m, 1H), 6.93 (d, J = 3.6 Hz, 1H), 6.54 (d, J = 15.9 Hz, 1H), 6.29 ( d, J = 3.6 Hz, 1H), 5.23 and 5.18 (each d, J = 14.4 Hz, each 1H), 4.33 (sept, J = 6.6 Hz, 1H), 2.39 (s, 3H), 2.34 (s, 3H), 1.06 and 1.00 (every d, J = 6.6 Hz, every 3H).

10 Ejemplo 5(38)Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilcinámico Example 5 (38) 4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylcinamic acid

15 TLC: Fr 0,46 (cloroformo:metanol = 9:1); RMN (DMSOd6): δ 7,88 (d, J = 8,1 Hz, I H), 7,84 (d, J = 8,4 Hz, 1H), 7,78 (s, 1H), 7,62-7,47 (m, 5H), 7,44-7,35 (m, 2H), 6,84 (d, J = 3,6 Hz, 1H), 6,54 (d, J = 16,2 Hz, 1H), 6,20 (d, J = 3,6 Hz, 1H), 5,35-4,90 (a, 2H), 3,47 (d, J = 7,2 Hz, 2H), 2,35 (s, 3H), 2,14 (s, 3H), 1,63-1,49 (m, 1H), 0,83 (d, J = 6,3 Hz, 6H). TLC: Fr 0.46 (chloroform: methanol = 9: 1); NMR (DMSOd6): δ 7.88 (d, J = 8.1 Hz, IH), 7.84 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.62 -7.47 (m, 5H), 7.44-7.35 (m, 2H), 6.84 (d, J = 3.6 Hz, 1H), 6.54 (d, J = 16.2 Hz, 1H), 6.20 (d, J = 3.6 Hz, 1H), 5.35-4.90 (a, 2H), 3.47 (d, J = 7.2 Hz, 2H), 2.35 (s, 3H), 2.14 (s, 3H), 1.63-1.49 (m, 1H), 0.83 (d, J = 6.3 Hz, 6H).

20 Ejemplo 5(39)Ácido 4-[3-[N-isobutil-N-[2-(4-metiltiazolil)sulfonil]amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (39) 4- [3- [N-Isobutyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

25 TLC: Fr 0,71 (acetato de etilo : metanol = 9:1); RMN: δ 7,82-7,71 (m, 4H), 7,51-7,46 (m, 1H), 7,43-7,32 (m, 4H), 7,21 (s, 1H), 6,95 (s, 1H), 6,48 (d, J = 16,2 Hz, 1H), 5,04 y 4,91 (cada m a, total 2H), 3,83-3,60 (m a, 2H), 2,38 (s, 3H), 2,34 (s, 3H), 1,81 -1,67 (m, 1H), 0,95 (s a, 6H). TLC: Fr 0.71 (ethyl acetate: methanol = 9: 1); NMR: δ 7.82-7.71 (m, 4H), 7.51-7.46 (m, 1H), 7.43-7.32 (m, 4H), 7.21 (s, 1H) , 6.95 (s, 1H), 6.48 (d, J = 16.2 Hz, 1H), 5.04 and 4.91 (each ma, total 2H), 3.83-3.60 (ma , 2H), 2.38 (s, 3H), 2.34 (s, 3H), 1.81 -1.67 (m, 1H), 0.95 (sa, 6H).

30 Ejemplo 5(40) Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico Example 5 (40) 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid

TLC: Fr 0,71 (acetato de etilo : metanol = 9:1); RMN (DMSO-d6): δ 7,88-7,83 (m, 2H), 7,65-7,47 (m, 8H), 7,42-7,37 (m, 1H), 6,55 (d, J = 15,9 Hz, 1H), 5,16 (s, 2H), 4,62-4,49 (m, 1H), 2,42 (s, 3H), 2,36 (s, 3H), 1,13 (d, J = 6,6 Hz, 3H), 1,03 (d, J = 6,6 Hz, 3H). TLC: Fr 0.71 (ethyl acetate: methanol = 9: 1); NMR (DMSO-d6): δ 7.88-7.83 (m, 2H), 7.65-7.47 (m, 8H), 7.42-7.37 (m, 1H), 6.55 (d, J = 15.9 Hz, 1H), 5.16 (s, 2H), 4.62-4.49 (m, 1H), 2.42 (s, 3H), 2.36 (s, 3H), 1.13 (d, J = 6.6 Hz, 3H), 1.03 (d, J = 6.6 Hz, 3H).

Ejemplo 5(41) Ácido 4-[6-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 5 (41) 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

10 TLC: Fr 0,34 (diclorometano:metanol = 19:1); RMN: δ 8,10 (d, J = 8,4 Hz, 2H), 7,35 (d, J = 8,4 Hz, 2H), 7,14 (s, 1H), 6,90 (s a, 1H), 6,79 (s, 1H), 4,92 (m, 2H), 4,20-3,60 (m, 2H), 2,90-2,83 (m, 4H), 2,33 (s, 3H), 2,09 (m, 2H), 1,20 (t, J = 7,2 Hz, 3H). 10 TLC: Rf 0.34 (dichloromethane: methanol = 19: 1); NMR: δ 8.10 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.14 (s, 1H), 6.90 (s, 1H), 6.79 (s, 1H), 4.92 (m, 2H), 4.20-3.60 (m, 2H), 2.90-2.83 (m, 4H), 2.33 (s, 3H), 2.09 (m, 2H), 1.20 (t, J = 7.2 Hz, 3H).

15 Ejemplo 5(42) Ácido 4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-propilamino]indan-5-iloximetil]benzoico Example 5 (42) 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid

20 TLC: Fr 0,34 (diclorometano:metanol = 19:1); RMN: δ 8,11 (d, J = 8,4 Hz, 2H), 7,35 (d, J = 8,4 Hz, 2H), 7,15 (s, 1H), 6,90 (s a, 1H), 6,78 (s, 1H), 5,10-4,70 (m, 2H), 4,00-3,50 (m, 2H), 2,90-2,84 (m, 4H), 2,32 (s, 3H), 2,09 (m, 2H), 1,58 (m, 2H), 0,93 (t, J = 7,5 Hz, 3H). TLC: Fr 0.34 (dichloromethane: methanol = 19: 1); NMR: δ 8.11 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.15 (s, 1H), 6.90 (s, 1H), 6.78 (s, 1H), 5.10-4.70 (m, 2H), 4.00-3.50 (m, 2H), 2.90-2.84 (m, 4H) , 2.32 (s, 3H), 2.09 (m, 2H), 1.58 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H).

Ejemplo 5(43)25 Ácido 4-[4,5-dimetil-2-(N-(5-metil-2-furilsulfonil)-N-(2-provenil)amino]fenoximetil]benzoico Example 5 (43) 25 4- [4,5-Dimethyl-2- (N- (5-methyl-2-furylsulfonyl) -N- (2-provenyl) amino] phenoxymethyl] benzoic acid

TLC: Fr 0,44 (cloroformo:metanol = 9:1); TLC: Fr 0.44 (chloroform: methanol = 9: 1);

30 RMN: δ 8,12 (d, J = 8,4 Hz, 2H), 7,43 (d, J = 8,4 Hz, 2H), 7,01 (s, 1H), 6,77 (d, J = 3,0 Hz, 1H), 6,68 (s, 1H), 5,995,94 (m, 1H), 5,92-5,75 (m, 1H), 5,16-5,03 (m, 2H), 5,02 (s, 2H), 4,42-4,20 (m, 2H), 2,21 (s, 3M, 2,17 (s, 3H), 2,15 (s, 3H). 30 NMR: δ 8.12 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.01 (s, 1H), 6.77 (d , J = 3.0 Hz, 1H), 6.68 (s, 1H), 5,995.94 (m, 1H), 5.92-5.75 (m, 1H), 5.16-5.03 ( m, 2H), 5.02 (s, 2H), 4.42-4.20 (m, 2H), 2.21 (s, 3M, 2.17 (s, 3H), 2.15 (s, 3H).

Ejemplo 5(45) Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metilbenzoico Example 5 (45) 4- [4,5-dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid

5 TLC: Fr 0,42 (cloroformo:metanol = 9:1); RMN: δ 7,97-7,90 (m, 2H), 7,45 (d, J = 8,1 Hz, 1H), 7,01 (s, 1H), 6,76 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 5,95 (m, 1H), 4,96 (s, 2H), 3,52-3,66 (a, 2H), 2,37 (s, 3H), 2,25 (s, 3H), 2,19 (s, 3H), 2,13 (s, 3H), 1,14 (t, J = 7,2 Hz, 3H). 5 TLC: Fr 0.42 (chloroform: methanol = 9: 1); NMR: δ 7.97-7.90 (m, 2H), 7.45 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H), 6.76 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 5.95 (m, 1H), 4.96 (s, 2H), 3.52-3.66 (a, 2H), 2.37 (s, 3H), 2.25 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H).

10 Ejemplo 5(46) Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-propilamino]fenoximetil]-3-metilbenzoico Example 5 (46) 4- [4,5-dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] phenoxymethyl] -3-methylbenzoic acid

15 TLC: Fr 0,42 (cloroformo:metanol = 9:1), RMN: δ 7,98-7,90 (m, 2H), 7,45 (d, J = 8,1 Hz, 1H), 7,02 (s, 1H), 6,78-6,70 (m, 2H), 5,95 (m, 1H), 4,95 (s, 2H), 3,713,55 (a, 2H), 2,37 (s, 3H), 2,24 (s, 3H), 2,19 (s, 3H), 2,12 (s, 3H), 1,60-1,44 (m, 2H), 0,88 (t, J = 7,5 Hz, 3H). 15 TLC: Fr 0.42 (chloroform: methanol = 9: 1), NMR: δ 7.98-7.90 (m, 2H), 7.45 (d, J = 8.1 Hz, 1H), 7 , 02 (s, 1H), 6.78-6.70 (m, 2H), 5.95 (m, 1H), 4.95 (s, 2H), 3,713.55 (a, 2H), 2, 37 (s, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 2.12 (s, 3H), 1.60-1.44 (m, 2H), 0.88 (t, J = 7.5 Hz, 3H).

Ejemplo 5(47)20 Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]fenoximetil]-3-metilbenzoico Example 5 (47) 20 4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] -3-methylbenzoic acid

TLC: Fr 0,45 (cloroformo:metanol = 9:1); 25 RMN: δ 7,98-7,90 (m, 2H), 7,45 (d, J = 8,1 Hz, 1H), 7,01 (s, 1H), 6,77 (d, J = 3,3 Hz, 1H), 6,71 (s, 1H), 5,96 (m, 1H), 5,83 (m, 1H), 5,15-5,00 (m, 2H), 4,96 (s, 2H), 4,40-4,20 (a, 2H), 2,38 (s, 3H), 2,23 (s, 3H), 2,18 (s, 3H), 2,14 (s, 3H). TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 7.98-7.90 (m, 2H), 7.45 (d, J = 8.1 Hz, 1H), 7.01 (s, 1H), 6.77 (d, J = 3.3 Hz, 1H), 6.71 (s, 1H), 5.96 (m, 1H), 5.83 (m, 1H), 5.15-5.00 (m, 2H), 4, 96 (s, 2H), 4.40-4.20 (a, 2H), 2.38 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H).

Ejemplo 5(48)Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil)-3-metilbenzoico 30 Example 5 (48) 4- [4,5-dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl) -3-methylbenzoic acid 30

TLC: Fr 0,41 (cloroformo:metanol = 9:1); RMN: δ 8,00-7,94 (m, 2H), 7,53 (d, J = 7,8 Hz, 1H), 6,80 (s, 1H), 6,77 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 6,01 (m, 1H), TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR: δ 8.00-7.94 (m, 2H), 7.53 (d, J = 7.8 Hz, 1H), 6.80 (s, 1H), 6.77 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.01 (m, 1H),

5,08 (d, J = 12,3 Hz, 1H), 5,00 (d, J = 12,3 Hz, 1H), 3,84 (d, J = 14,4 Hz, 1H), 3,56 (d, J = 14,4 Hz, 1H), 2,42 (s, 3H), 2,23 (s, 3H), 2,21 (s, 3H), 2,14 (s, 3H), 1,25 (s, 3H), 1,18 (s, 3H). 5.08 (d, J = 12.3 Hz, 1H), 5.00 (d, J = 12.3 Hz, 1H), 3.84 (d, J = 14.4 Hz, 1H), 3, 56 (d, J = 14.4 Hz, 1H), 2.42 (s, 3H), 2.23 (s, 3H), 2.21 (s, 3H), 2.14 (s, 3H), 1.25 (s, 3H), 1.18 (s, 3H).

Ejemplo 5(50) Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]-3-metilbenzoico Example 5 (50) 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid

TLC: Fr 0,32 (cloroformo:metanol = 10:1); TLC: Fr 0.32 (chloroform: methanol = 10: 1);

10 RMN: δ 7,97 (d, J = 7,8 Hz, 1H), 7,95 (s, 1H), 7,53 (d, J = 7,8 Hz, 1H), 6,89 (s, 1H), 6,86 (s, 1H), 6,75 (d, J = 3,3 Hz, 1H), 6,01 (dd, J = 3,3, 0,9 Hz, 1H), 5,08 (d, J = 12,9 Hz, 1H), 5,02 (d, J = 12,9 Hz, 1H), 3,85 (d, J = 14,7 Hz, 1H), 3,58 (d, J = 14,7 Hz, 1H), 2,90-2,78 (m, 4H), 2,42 (s, 3H), 2,21 (s, 3H), 2,13-2,01 (m, 2H), 1,25 (s, 3H), 1,18 (s, 3H). 10 NMR: δ 7.97 (d, J = 7.8 Hz, 1H), 7.95 (s, 1H), 7.53 (d, J = 7.8 Hz, 1H), 6.89 (s , 1H), 6.86 (s, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.01 (dd, J = 3.3, 0.9 Hz, 1H), 5 , 08 (d, J = 12.9 Hz, 1H), 5.02 (d, J = 12.9 Hz, 1H), 3.85 (d, J = 14.7 Hz, 1H), 3.58 (d, J = 14.7 Hz, 1H), 2.90-2.78 (m, 4H), 2.42 (s, 3H), 2.21 (s, 3H), 2.13-2, 01 (m, 2H), 1.25 (s, 3H), 1.18 (s, 3H).

Ejemplo 5(52)15 Ácido 4-[6-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico Example 5 (52) 15 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid

20 RMN (DMSOd6): δ 7,55 (d, J = 16,0 Hz, 1H), 7,50-7,40 (m, 3H), 7,19 (d, J = 8,1 Hz, 1H), 7,09 (s, 1H), 6,98 (s, 1H), 6,52 (d, J = 16,0 Hz, 1H), 4,84 (a, 2H), 3,66 (a, 2H), 2,85 (t, J = 7,4 Hz, 2H), 2,77 (t, J = 7,4 Hz, 2H), 2,23 (s, 3H), 2,19 (s, 3H), 2,10-1,90 (m, 2H), 1,01 (t, J = 7,0 Hz, 3H). NMR (DMSOd6): δ 7.55 (d, J = 16.0 Hz, 1H), 7.50-7.40 (m, 3H), 7.19 (d, J = 8.1 Hz, 1H ), 7.09 (s, 1H), 6.98 (s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 4.84 (a, 2H), 3.66 (a , 2H), 2.85 (t, J = 7.4 Hz, 2H), 2.77 (t, J = 7.4 Hz, 2H), 2.23 (s, 3H), 2.19 (s , 3H), 2.10-1.90 (m, 2H), 1.01 (t, J = 7.0 Hz, 3H).

Ejemplo 5(53)25 Ácido 4-[2-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 5 (53) 25 4- [2- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,41 (cloroformo:metanol = 9:1); TLC: Fr 0.41 (chloroform: methanol = 9: 1);

30 RMN: δ 8,11 (d, J = 8,4 Hz, 2H), 7,43 (d, J = 8,4 Hz, 2H), 7,09 (s, 1H), 6,74 (d, J = 3,0 Hz, 1H), 6,70 (s, 1H), 5,965,92 (m, 1H), 5,02 (s a, 2H), 3,68-3,40 (m, 2H), 2,23 (s, 3H), 2,19 (s, 3H), 2,14 (s, 3H), 1,03-0,86 (m, 1H), 0,46-0,35 (m, 2H), 0,21-0,06 (m, 2H). NMR: δ 8.11 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.09 (s, 1H), 6.74 (d , J = 3.0 Hz, 1H), 6.70 (s, 1H), 5.965.92 (m, 1H), 5.02 (sa, 2H), 3.68-3.40 (m, 2H) , 2.23 (s, 3H), 2.19 (s, 3H), 2.14 (s, 3H), 1.03-0.86 (m, 1H), 0.46-0.35 (m , 2H), 0.21-0.06 (m, 2H).

Ejemplo 5(54) Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil]benzoico Example 5 (54) 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] benzoic acid

5 TLC: Fr 0,34 (cloroformo:metanol = 9:1); RMN: δ 8,13 (d, J = 8,4 Hz, 2H), 7,52 (d, J = 8,4 Hz, 2H), 6,81 (s, 1H), 6,75 (s, 1H), 6,74 (d, J = 3,0 Hz, 1H), 6,035,98 (m, 1H), 5,22-4,96 (m, 2H), 3,92-3,76 y 3,64-3,48 (cada m, total 2H), 2,21 (s, 6H), 2,13 (s, 3H), 1,28 y 1,19 (cada s a, cada 3H). 5 TLC: Fr 0.34 (chloroform: methanol = 9: 1); NMR: δ 8.13 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 6.81 (s, 1H), 6.75 (s, 1H), 6.74 (d, J = 3.0 Hz, 1H), 6.035.98 (m, 1H), 5.22-4.96 (m, 2H), 3.92-3.76 and 3 , 64-3.48 (each m, total 2H), 2.21 (s, 6H), 2.13 (s, 3H), 1.28 and 1.19 (each sa, every 3H).

10 Ejemplo 5(55)Ácido 3-metil-4-[6-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 5 (55) 3-methyl-4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

15 TLC: Fr 0,60 (cloroformo:metanol = 9:1); RMN: δ 7,76 (d, J = 15,9 Hz, 1H), 7,42-7,34 (m, 2H), 7,27-7,22 (m, 1H), 7,12 (s, 1H), 6,92 (d, J = 0,9 Hz, 1H), 6,78 (s, 1H), 6,47 (d, J = 15,9 Hz, 1H), 4,90-4,72 (m, 4H), 4,50-4,14 (m, 2H), 2,92-2,80 (m, 4H), 2,31 (s, 6H), 2,18-2,00 (m, 2H), 1,81 (s, 3H). TLC: Fr 0.60 (chloroform: methanol = 9: 1); NMR: δ 7.76 (d, J = 15.9 Hz, 1H), 7.42-7.34 (m, 2H), 7.27-7.22 (m, 1H), 7.12 (s , 1H), 6.92 (d, J = 0.9 Hz, 1H), 6.78 (s, 1H), 6.47 (d, J = 15.9 Hz, 1H), 4.90-4 , 72 (m, 4H), 4.50-4.14 (m, 2H), 2.92-2.80 (m, 4H), 2.31 (s, 6H), 2.18-2.00 (m, 2H), 1.81 (s, 3H).

20 Ejemplo 5(56)Ácido 4-[6-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico Example 5 (56) 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid

25 TLC: Fr 0,60 (cloroformo:metanol = 9:1); RMN: δ 7,77 (d, J = 15,9 Hz, 1H), 7,42-7,38 (m, 2H), 7,30-7,25 (m, 1H), 7,21 (s, 1H), 6,89 (d, J = 0,9 Hz, 1H), 6,82 (s, 1H), 6,46 (d, J = 15,9 Hz, 1H), 4,92-4,64 (m, 2H), 3,84-3,42 (m, 2H), 2,95-2,76 (m, 4H), 2,31 (s, 3H), 2,31 (s, 3H), 2,18-2,02 (m, 2H), 1,08-0,90 (m, 1H), 0,46-0,40 (m, 2H), 0,26-0,08 (m, 2H). 25 TLC: Fr 0.60 (chloroform: methanol = 9: 1); NMR: δ 7.77 (d, J = 15.9 Hz, 1H), 7.42-7.38 (m, 2H), 7.30-7.25 (m, 1H), 7.21 (s , 1H), 6.89 (d, J = 0.9 Hz, 1H), 6.82 (s, 1H), 6.46 (d, J = 15.9 Hz, 1H), 4.92-4 , 64 (m, 2H), 3.84-3.42 (m, 2H), 2.95-2.76 (m, 4H), 2.31 (s, 3H), 2.31 (s, 3H ), 2.18-2.02 (m, 2H), 1.08-0.90 (m, 1H), 0.46-0.40 (m, 2H), 0.26-0.08 (m , 2H).

30 Ejemplo 5(57)Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 5 (57) 4- [6- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,46 (cloroformo:metanol = 9:1); RMN: δ 7,78 (d, J = 15, 9 Hz, 1H), 7,58 (d, J = 8,1 Hz, 2H), 7,47 (d, J = 8,1 Hz, 2H), 6,85 (d, J = 3,6 Hz, 2H), 6,74 (d, TLC: Fr 0.46 (chloroform: methanol = 9: 1); NMR: δ 7.78 (d, J = 15, 9 Hz, 1H), 7.58 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H) , 6.85 (d, J = 3.6 Hz, 2H), 6.74 (d,

5 J = 3,6 Hz, 1H), 6,47 (d, J = 15,9 Hz, 1H), 6,01 (d, J = 2,1 Hz, 1H), 5,10 (d, J = 12,0 Hz, 1H),4,99 (d, J = 12,0 Hz, 1H), 3,85 (d, J = 14,1 Hz, 1H), 3,53 (d, J = 14,1 Hz, 1H), 2,90-2,77 (m, 4H), 2,23 (s, 3H), 2,07 (m, 2H), 1,27 (s, 3H), 1,16 (s, 3H). 5 J = 3.6 Hz, 1H), 6.47 (d, J = 15.9 Hz, 1H), 6.01 (d, J = 2.1 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 4.99 (d, J = 12.0 Hz, 1H), 3.85 (d, J = 14.1 Hz, 1H), 3.53 (d, J = 14 , 1 Hz, 1H), 2.90-2.77 (m, 4H), 2.23 (s, 3H), 2.07 (m, 2H), 1.27 (s, 3H), 1.16 (s, 3H).

Ejemplo 5(58)10 Ácido 3-metil-4-[6-[N-(4-metil-2-tiazolilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]cinámico Example 5 (58) 10 3-Methyl-4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid

TLC: Fr 0,42 (diclorometano:metanol = 10:1); TLC: Fr 0.42 (dichloromethane: methanol = 10: 1);

15 RMN: δ 7,76 (d, J = 15,9 Hz, 1H), 7,42-7,36 (m, 2H), 7,28 (m, 1H), 7,11 (s, 1H), 6,92 (m, 1H), 6,80 (s, 1H), 6,47 (d, J = 15,9 Hz, 1H), 5,87 (m, 1H), 5,11 (dd, J = 17,1, 1,5 Hz, 1H), 5,07 (dd, J = 8,7, 1,5 Hz, 1H), 4,83 (a, 2H), 4,32 (a, 2H), 2,92-2,82 (m, 4H), 2,33 (d, J = 0,6 Hz, 3H), 2,32 (s, 3H), 2,16-2,04 (m, 2H). NMR: δ 7.76 (d, J = 15.9 Hz, 1H), 7.42-7.36 (m, 2H), 7.28 (m, 1H), 7.11 (s, 1H) , 6.92 (m, 1H), 6.80 (s, 1H), 6.47 (d, J = 15.9 Hz, 1H), 5.87 (m, 1H), 5.11 (dd, J = 17.1, 1.5 Hz, 1H), 5.07 (dd, J = 8.7, 1.5 Hz, 1H), 4.83 (a, 2H), 4.32 (a, 2H ), 2.92-2.82 (m, 4H), 2.33 (d, J = 0.6 Hz, 3H), 2.32 (s, 3H), 2.16-2.04 (m, 2H).

Ejemplo 5(59)20 Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]-3-metilcinámico Example 5 (59) 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid

25 RMN: δ 7,76 (d, J = 15,9 Hz, 1H), 7,44-7,38 (m, 3H), 7,05 (m, 1H), 6,88 (s, 1H), 6,82 (s, 1H), 6,46 (d, J = 15,9 Hz, 1H), 5,03 (d, J = 12,0 Hz, 1H), 4,93 (d, J = 12,0 Hz, 1H), 3,96 (d, J = 14,4 Hz, 1H), 3,69 (d, J = 14,4 Hz, 1H), 2,87 (t, J = 7,5 Hz, 2H), 2,77 (t, J = 7,5 Hz, 2H), 2,43 (s, 3H), 2,40 (s, 3H), 2,13-2,00 (m, 2H), 1,23 (s, 3H), 1,18 (s, 3H). NMR: δ 7.76 (d, J = 15.9 Hz, 1H), 7.44-7.38 (m, 3H), 7.05 (m, 1H), 6.88 (s, 1H) , 6.82 (s, 1H), 6.46 (d, J = 15.9 Hz, 1H), 5.03 (d, J = 12.0 Hz, 1H), 4.93 (d, J = 12.0 Hz, 1H), 3.96 (d, J = 14.4 Hz, 1H), 3.69 (d, J = 14.4 Hz, 1H), 2.87 (t, J = 7, 5 Hz, 2H), 2.77 (t, J = 7.5 Hz, 2H), 2.43 (s, 3H), 2.40 (s, 3H), 2.13-2.00 (m, 2H), 1.23 (s, 3H), 1.18 (s, 3H).

Ejemplo 5(60)30 Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]fenoximetil-1-3-metilbenzoico Example 5 (60) 30 4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl-1-3-methylbenzoic acid

TLC: Fr 0,45 (cloroformo:metanol = 9:1); RMN: δ 8,00-7,92 (m, 2H), 7,47 (d, J = 7,8 Hz, 1H), 7,09 (s, 1H), 6,78-6,71 (m, 2H), 5,94 (m, 1H), 4,96 (s, 2H), 3,633,45 (a, 2H), 2,37 (s, 3H), 2,25 (s, 3H), 2,19 (s, 3H), 2,13 (s, 3H), 0,95 (m, 1H), 0,44-0,35 (m, 2H), 0,15-0,22 (m, 2H). TLC: Fr 0.45 (chloroform: methanol = 9: 1); NMR: δ 8.00-7.92 (m, 2H), 7.47 (d, J = 7.8 Hz, 1H), 7.09 (s, 1H), 6.78-6.71 (m , 2H), 5.94 (m, 1H), 4.96 (s, 2H), 3,633.45 (a, 2H), 2.37 (s, 3H), 2.25 (s, 3H), 2 , 19 (s, 3H), 2.13 (s, 3H), 0.95 (m, 1H), 0.44-0.35 (m, 2H), 0.15-0.22 (m, 2H ).

Ejemplo 5(61) Ácido 3-metil-4-[6-(N-(4-metil-2-tiazolilsulfonil)-N-propilamino]indan-5-iloximetil]cinámico Example 5 (61) 3-Methyl-4- [6- (N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid

10 TLC: Fr 0,41 (cloroformo:metanol = 9:1); RMN: δ 7,76 (d, J = 16,2 Hz, 1H), 7,44-7,34 (m, 2H), 7,32-7,20 (m, 1H), 7,13 (s, 1H), 6,90 (s, 1H), 6,82 (s, 1H), 6,46 (d, J = 16,2 Hz, 1H), 4,90-4,70 (m, 2H), 3,90-3,50 (m, 2H), 2,89 (t, J = 7,5 Hz) y 2,86 (t, J = 7,5 Hz) total 4H, 2,31 (s) y 2,30 (s) total 6H, 2,09 (quint, J = 7,5 Hz, 2H), 1,58 (m, 2H), 0,91 (t, J = 7,5 Hz, 3H). 10 TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR: δ 7.76 (d, J = 16.2 Hz, 1H), 7.44-7.34 (m, 2H), 7.32-7.20 (m, 1H), 7.13 (s , 1H), 6.90 (s, 1H), 6.82 (s, 1H), 6.46 (d, J = 16.2 Hz, 1H), 4.90-4.70 (m, 2H) , 3.90-3.50 (m, 2H), 2.89 (t, J = 7.5 Hz) and 2.86 (t, J = 7.5 Hz) total 4H, 2.31 (s) and 2.30 (s) total 6H, 2.09 (quint, J = 7.5 Hz, 2H), 1.58 (m, 2H), 0.91 (t, J = 7.5 Hz, 3H) .

15 Ejemplo 5(62) Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 5 (62) 4- [6- [N- (2-hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

20 TLC: Fr 0,29 (diclorometano:metanol = 19:1); RMN: δ 8,13 (d, J = 7,8 Hz, 2H), 7,48 (d, J = 7,8 Hz, 2H), 7,02 (s a, 1H), 6,90 (s, 1H), 6,83 (s, 1H), 5,12(d, J = 12,6 Hz, 1H), 4,95 (d, J = 12,6 Hz, 1H), 3,96(d, J = 15,0 Hz, 1H), 3,77 (d, J = 15,0 Hz, 1H), 2,88-2,75 (m, 4H), 2,42 (s, 3H), 2,06 (m,2H), 1,29 (s, 3H), 1,22 (s, 3H). TLC: Fr 0.29 (dichloromethane: methanol = 19: 1); NMR: δ 8.13 (d, J = 7.8 Hz, 2H), 7.48 (d, J = 7.8 Hz, 2H), 7.02 (sa, 1H), 6.90 (s, 1H), 6.83 (s, 1H), 5.12 (d, J = 12.6 Hz, 1H), 4.95 (d, J = 12.6 Hz, 1H), 3.96 (d, J = 15.0 Hz, 1H), 3.77 (d, J = 15.0 Hz, 1H), 2.88-2.75 (m, 4H), 2.42 (s, 3H), 2, 06 (m, 2H), 1.29 (s, 3H), 1.22 (s, 3H).

25 Ejemplo 6 Sal sódica del ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 6 Sodium salt of 3-methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic

30 A una suspensión del compuesto preparado en el Ejemplo 2(74) (213 g) en etanol (2 l), se le añadió una solución acuosa 5 N de hidróxido sódico (74,7 ml) y la mezcla se agitó durante 0,5 horas a 80 ºC. La solución de reacción se filtró con calentamiento para retirar los extractos insolubles, después la mezcla se enfrió y el precipitado se recogió. El licor madre se concentró y el residuo se disolvió en etanol (500 ml) y agua (25 ml) con calentamiento. La mezcla se filtró con calentamiento para retirar los extractos insolubles, después la mezcla se enfrió y el precipitado se To a suspension of the compound prepared in Example 2 (74) (213 g) in ethanol (2 L), a 5 N aqueous solution of sodium hydroxide (74.7 ml) was added and the mixture was stirred for 0, 5 hours at 80 ° C. The reaction solution was filtered with heating to remove insoluble extracts, then the mixture was cooled and the precipitate was collected. The mother liquor was concentrated and the residue was dissolved in ethanol (500 ml) and water (25 ml) with heating. The mixture was filtered with heating to remove insoluble extracts, then the mixture was cooled and the precipitate was

35 recogió. Con calentamiento, todos los sólidos recogidos se secaron a presión reducida para dar el compuesto de la presente invención (165 g) que tenía los siguientes datos físicos. TLC: Fr 0,52 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,49 (s, 1H), 7,29 (s, 1H), 7,26 (d, J = 8,1 Hz, 1H), 7,10-7,00 (m, 4H), 6,38 (d, J = 15,9 Hz, 1H), 4,89 (d a, J = 10, 5 Hz, 1H), 4,63 (d a, J = 10,5 Hz, 1H), 3,55-3,25 (m, 2H), 2,85 (t, J = 7,2 Hz, 2H), 2,78 (t, J = 7,2 35 picked up. With heating, all collected solids were dried under reduced pressure to give the compound of the present invention (165 g) having the following physical data. TLC: Fr 0.52 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.49 (s, 1H), 7.29 (s, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.10-7.00 ( m, 4H), 6.38 (d, J = 15.9 Hz, 1H), 4.89 (da, J = 10, 5 Hz, 1H), 4.63 (da, J = 10.5 Hz, 1H), 3.55-3.25 (m, 2H), 2.85 (t, J = 7.2 Hz, 2H), 2.78 (t, J = 7.2

40 Hz, 2H), 2,21 (s, 3H), 2,18 (s, 3H), 2,10-1,90 (m, 2H), 1,60-1,45 (m, 1H), 1,00-0,70 (m, 6H). 40 Hz, 2H), 2.21 (s, 3H), 2.18 (s, 3H), 2.10-1.90 (m, 2H), 1.60-1.45 (m, 1H), 1.00-0.70 (m, 6H).

Ejemplo 6(1) Sal sódica del ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-5-trifluorometilfenoximetil]benzoico Example 6 (1) 4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -5-trifluoromethylphenoxymethyl] benzoic acid sodium salt

5 TLC: Fr 0,50 (cloroformo:metanol = 9:1); RMN: δ 7,84 (d, J = 8,1 Hz, 2H), 7,20-6,95 (m, 5H), 6,65 (d, J = 3,3 Hz, 1H), 5,84 (d, J = 3,3 Hz, 1H), 4,75 (s a, 2H), 4,30-4,10 (m, 1H), 2,12 (s, 3H), 0,86 (d a, J = 3,9 Hz, 6H). 5 TLC: Fr 0.50 (chloroform: methanol = 9: 1); NMR: δ 7.84 (d, J = 8.1 Hz, 2H), 7.20-6.95 (m, 5H), 6.65 (d, J = 3.3 Hz, 1H), 5, 84 (d, J = 3.3 Hz, 1H), 4.75 (sa, 2H), 4.30-4.10 (m, 1H), 2.12 (s, 3H), 0.86 (da , J = 3.9 Hz, 6H).

10 Ejemplo 6(2) Sal sódica del ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 6 (2) Sodium salt of 4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

15 TLC: Fr 0,40 (cloroformo:metanol = 9:1); RMN: δ 7,83 (d, J = 8,1 Hz, 2H), 7,00 (d, J = 8,1 Hz, 2H), 6,88 (s, 1H), 6,59 (s, 1H), 6,54 (d, J = 3,0 Hz, 1H), 5,74 (s, 1H), 4,90-4,50 (m, 2H), 3,33 (d a, J = 6,3 Hz, 2H), 2,09 (s, 3H), 2,05 (s, 3H), 1,93 (s, 3H), 1,60-1,40 (m, 1H), 0,73 (d, J = 6,3 Hz, 6H). TLC: Fr 0.40 (chloroform: methanol = 9: 1); NMR: δ 7.83 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 6.88 (s, 1H), 6.59 (s, 1H), 6.54 (d, J = 3.0 Hz, 1H), 5.74 (s, 1H), 4.90-4.50 (m, 2H), 3.33 (da, J = 6 , 3 Hz, 2H), 2.09 (s, 3H), 2.05 (s, 3H), 1.93 (s, 3H), 1.60-1.40 (m, 1H), 0.73 (d, J = 6.3 Hz, 6H).

20 Ejemplo 6(3) Sal sódica del ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico Example 6 (3) Sodium salt of 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

25 TLC: Fr 0,41 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,70 (s, 1H), 7,66 (d, J = 7,8 Hz, 1H), 7,13 (d, J = 7,8 Hz, 1H), 6,99 (s, 1H), 6,91 (s, 1H), 6,76 (d, J = 3,3 Hz, 1H), 6,14 (d, J = 3,3 Hz, 1H), 4,88 (s a, 2H), 3,36 (d, J = 6,9 Hz, 2H), 2,26 (s, 3H), 2,22 (s, 3H), 2,14 (s, 3H), 2,10 (s, 3H), 1,60-1,45 (m, 1H), 0,81 (d a, J = 6,3 Hz, 6H). 25 TLC: Fr 0.41 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.70 (s, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.13 (d, J = 7.8 Hz, 1H), 6 , 99 (s, 1H), 6.91 (s, 1H), 6.76 (d, J = 3.3 Hz, 1H), 6.14 (d, J = 3.3 Hz, 1H), 4 , 88 (sa, 2H), 3.36 (d, J = 6.9 Hz, 2H), 2.26 (s, 3H), 2.22 (s, 3H), 2.14 (s, 3H) , 2.10 (s, 3H), 1.60-1.45 (m, 1H), 0.81 (da, J = 6.3 Hz, 6H).

30 Ejemplo 6(4) Sal sódica del ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 6 (4) Sodium salt of 4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

35 TLC: Fr 0,40 (cloroformo:metanol = 9:1); RMN (CD3OD): δ 7,91 (d, J = 8,1 Hz, 2H), 7,19 (s, 1H), 7,18 (d, J = 8,1 Hz, 2H), 7,13 (s, 1H), 6,93 (s, 1H), 5,00-4,80 (m, 1H), 4,65-4,58 (m, 1H), 3,65-3,48 (m, 2H), 2,95-2,80 (m, 4H), 2,21 (d, J = 0,9 Hz, 3H), 2,09 (quint, J = 7,5 Hz, 2H), 1,66 (m, 1H), 1,03-0,85 (m, 6H). TLC: Fr 0.40 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 7.91 (d, J = 8.1 Hz, 2H), 7.19 (s, 1H), 7.18 (d, J = 8.1 Hz, 2H), 7.13 (s, 1H), 6.93 (s, 1H), 5.00-4.80 (m, 1H), 4.65-4.58 (m, 1H), 3.65-3.48 (m , 2H), 2.95-2.80 (m, 4H), 2.21 (d, J = 0.9 Hz, 3H), 2.09 (quint, J = 7.5 Hz, 2H), 1 , 66 (m, 1H), 1.03-0.85 (m, 6H).

Ejemplo 6(5) Sal potásica del ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico Example 6 (5) Potassium salt of 4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

10 TLC: Fr 0,37 (cloroformo:metanol = 9:1); RMN (DMSO-d6): δ 7,81 (d, J = 8,0 Hz, 2H), 7,47 (c, J = 0,4 Hz, 1H), 7,06 (d, J = 8,0 Hz, 1H), 7,03 (s, 2H), 6,95 (s, 1H), 5,10-4,80 (m, 1H), 4,80-4,50 (m, 1H), 3,43 (s a, 2H), 2,80 (c, J = 7,0 Hz, 4H), 2,23 (d, J = 0,4 Hz, 3H), 2,01 (c, J = 7,0 Hz, 2H), 1,53 (sept, J = 6,6 Hz, 1H), 0,85 (s a, 6H). TLC: Fr 0.37 (chloroform: methanol = 9: 1); NMR (DMSO-d6): δ 7.81 (d, J = 8.0 Hz, 2H), 7.47 (c, J = 0.4 Hz, 1H), 7.06 (d, J = 8, 0 Hz, 1H), 7.03 (s, 2H), 6.95 (s, 1H), 5.10-4.80 (m, 1H), 4.80-4.50 (m, 1H), 3.43 (sa, 2H), 2.80 (c, J = 7.0 Hz, 4H), 2.23 (d, J = 0.4 Hz, 3H), 2.01 (c, J = 7 , 0 Hz, 2H), 1.53 (sept, J = 6.6 Hz, 1H), 0.85 (sa, 6H).

15 Ejemplo 6(6) Sal sódica del ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico Example 6 (6) Sodium salt of 4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic

20 TLC: Fr 0,51 (cloroformo:metanol = 9:1); RMN: δ 7,37 (d, J = 15,9 Hz, 1H), 7,17 (d, J = 7,5 Hz, 2H), 7,10-6,90 (m, 3H), 6,67 (s, 1H), 6,55 (s, 1H), 6,45 (d, J = 15,9 Hz, 1H), 5,74 (s, 1H), 4,80-4,45 (m, 2H), 3,35 (d, J = 6,3 Hz, 2H), 2,85-2,55 (m, 4H), 2,10-1,80 (m, 5H), 1,651,40 (m, 1H), 0,74 (s a, 6H). TLC: Fr 0.51 (chloroform: methanol = 9: 1); NMR: δ 7.37 (d, J = 15.9 Hz, 1H), 7.17 (d, J = 7.5 Hz, 2H), 7.10-6.90 (m, 3H), 6, 67 (s, 1H), 6.55 (s, 1H), 6.45 (d, J = 15.9 Hz, 1H), 5.74 (s, 1H), 4.80-4.45 (m , 2H), 3.35 (d, J = 6.3 Hz, 2H), 2.85-2.55 (m, 4H), 2.10-1.80 (m, 5H), 1,651.40 ( m, 1H), 0.74 (sa, 6H).

25 Ejemplo 6(7) Sal sódica del ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico Example 6 (7) Sodium salt of 3-methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid

30 TLC: Fr 0,60 (cloroformo:metanol = 9: 1); RMN (CD3OD): δ 7,78 (s) y 7,75 (d, J = 8,1 Hz) total 2H, 7,24 (d, J = 8,1 Hz, 1H), 7,07 (s, 1H), 6,97 (s, 1H), 6,64 (d, J = 3,3 Hz, 1H), 6,03 (dd, J = 3,3, 0,9 Hz, 1H), 5,08-4,75 (m, 2H), 3,48 (d, J = 7,5 Hz, 2H), 2,94-2,80 (m, 4H), 2,32 (s, 3H), 2,15-2,00 (m) y 2,04 (s) total 5H, 1,87 (m, 1H), 0,98-0,80 (m, 6H). TLC: Fr 0.60 (chloroform: methanol = 9: 1); NMR (CD3OD): δ 7.78 (s) and 7.75 (d, J = 8.1 Hz) total 2H, 7.24 (d, J = 8.1 Hz, 1H), 7.07 (s , 1H), 6.97 (s, 1H), 6.64 (d, J = 3.3 Hz, 1H), 6.03 (dd, J = 3.3, 0.9 Hz, 1H), 5 , 08-4.75 (m, 2H), 3.48 (d, J = 7.5 Hz, 2H), 2.94-2.80 (m, 4H), 2.32 (s, 3H), 2.15-2.00 (m) and 2.04 (s) total 5H, 1.87 (m, 1H), 0.98-0.80 (m, 6H).

35 Ejemplo 6(8) Sal potásica del ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico Example 6 (8) Potassium salt of 4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic

TLC: Fr 0,36 (cloroformo:metanol = 9:1); RMN: δ 7,27 (d, J = 15,9 Hz, 1H), 7,21 (d, J = 7,5 Hz, 2H), 6,98 (d, J = 7,5 Hz, 2H), 6,84 (s, 1H), 6,78 (s, 1H), 6,70 (s, 5 1H), 6,41 (d, J = 15,9 Hz, 1H), 4,70-4,40 (m, 3H), 2,85-2,60 (m, 4H), 2,24 (s, 3H), 2,05-1,90 (m, 2H), 1,01 (d, J = 6,6 Hz, 3H), 0,95 (d, J = 6,6 Hz, 3H). TLC: Fr 0.36 (chloroform: methanol = 9: 1); NMR: δ 7.27 (d, J = 15.9 Hz, 1H), 7.21 (d, J = 7.5 Hz, 2H), 6.98 (d, J = 7.5 Hz, 2H) , 6.84 (s, 1H), 6.78 (s, 1H), 6.70 (s, 5 1H), 6.41 (d, J = 15.9 Hz, 1H), 4.70-4 , 40 (m, 3H), 2.85-2.60 (m, 4H), 2.24 (s, 3H), 2.05-1.90 (m, 2H), 1.01 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.6 Hz, 3H).

Ejemplo 6(9) Example 6 (9)

Sal potásica del ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 10 Potassium salt of 4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid

TLC: Fr 0,32 (cloroformo:metanol = 9:1); TLC: Fr 0.32 (chloroform: methanol = 9: 1);

RMN: δ 7,82 (d, J = 8,1 Hz, 2H), 7,33 (d, J = 3,0 Hz, 1H), 7,15 (d, J = 3,0 Hz, 1H), 6,94 (s, 1H), 6,89 (d, J = 8,1 Hz, 15 2H), 6,56 (s, 1H), 4,70-4,55 (m, 1H), 4,45-4,25 (m, 1H), 3,60-3,30 (m, 2H), 2,09 (s, 6H), 1,60-1,45 (m, 1H), 0,78 (s a, NMR: δ 7.82 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 3.0 Hz, 1H), 7.15 (d, J = 3.0 Hz, 1H) , 6.94 (s, 1H), 6.89 (d, J = 8.1 Hz, 15 2H), 6.56 (s, 1H), 4.70-4.55 (m, 1H), 4 , 45-4.25 (m, 1H), 3.60-3.30 (m, 2H), 2.09 (s, 6H), 1.60-1.45 (m, 1H), 0.78 (sa,

3H), 0,72 (s a, 3H). 3H), 0.72 (s a, 3H).

Ejemplo 6(10) Example 6 (10)

Sal sódica del ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 20 3-Methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid sodium salt

RMN (DMSO-d6): δ 7,98 (d, J = 3,0 Hz, 1H), 7,82 (d, J = 3,0 Hz, 1H), 7,64 (s, 1H), 7,60 (d, J = 7,8 Hz, 1H), 6,99 (d, J 25 = 7,8 Hz, 1H), 6,97 (s, 1H), 6,91 (s, 1H), 5,00-4,54 (m, 2H), 3,42 (d, J = 6,3 Hz, 2H), 2,20 (s, 3H), 2,20 (s, 3H), 2,11 NMR (DMSO-d6): δ 7.98 (d, J = 3.0 Hz, 1H), 7.82 (d, J = 3.0 Hz, 1H), 7.64 (s, 1H), 7 , 60 (d, J = 7.8 Hz, 1H), 6.99 (d, J 25 = 7.8 Hz, 1H), 6.97 (s, 1H), 6.91 (s, 1H), 5.00-4.54 (m, 2H), 3.42 (d, J = 6.3 Hz, 2H), 2.20 (s, 3H), 2.20 (s, 3H), 2.11

(s, 3H), 1,50 (m, 1H), 0,90-0,73 (m, 6H). (s, 3H), 1.50 (m, 1H), 0.90-0.73 (m, 6H).

Ejemplo 7 Example 7

Alcohol 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbencílico 30 4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzyl alcohol 30

A una suspensión del compuesto preparado en el Ejemplo 2(33) (1,20 g) en tetrahidrofurano (10 ml), se le añadió complejo de borohidruro-dimetiltiol (solución 2 M en tetrahidrofurano, 6,0 ml) y la mezcla se agitó durante 1 hora. A la To a suspension of the compound prepared in Example 2 (33) (1.20 g) in tetrahydrofuran (10 ml), borohydride dimethylthiol complex (2M solution in tetrahydrofuran, 6.0 ml) was added and the mixture was stirred for 1 hour. To

mezcla de reacción, se le añadieron metanol, agua y ácido clorhídrico 1 N y se extrajo con acetato de etilo dos veces. La fase orgánica combinada se lavó sucesivamente con ácido clorhídrico 1 N, agua y una solución acuosa saturada de cloruro sódico, se secó sobre sulfato sódico anhidro y se purificó por cromatografía en columna sobre gel de sílice (n-hexano:acetato de etilo = de 8:1 a 2:1), dando el compuesto de la presente invención (947 mg) que tenía los siguientes datos físicos. TLC: Fr 0,57 (n-hexano:acetato de etilo = 1:1); RMN: δ 7,20 (d, J = 7,8 Hz, 1H), 7,13 (s, 1H), 7,10 (d, J = 7,8 Hz, 1H), 7,07 (s, 1H), 6,95 (s, 1H), 6,79 (d, J = 3,3 Hz, 1H), 6,20-6,15 (m, 1H), 4,94 (a, 1H), 4,83 (a, 1H), 4,45 (s, 2H), 3,32 (d, J = 6,9 Hz, 2H), 2,84 (t, J = 7,4 Hz, 2H), 2,78 (t, J = 7,4 Hz, 2H), 2,25 (s, 3H), 2,13 (s, 3H), 2,10-1,90 (m, 2H), 1,55-1,40 (m, 1H), 0,90-0,70 (m, 6H). reaction mixture, methanol, water and 1 N hydrochloric acid were added and extracted with ethyl acetate twice. The combined organic phase was washed successively with 1 N hydrochloric acid, water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and purified by column chromatography on silica gel (n-hexane: ethyl acetate = de 8: 1 to 2: 1), giving the compound of the present invention (947 mg) that had the following physical data. TLC: Fr 0.57 (n-hexane: ethyl acetate = 1: 1); NMR: δ 7.20 (d, J = 7.8 Hz, 1H), 7.13 (s, 1H), 7.10 (d, J = 7.8 Hz, 1H), 7.07 (s, 1H), 6.95 (s, 1H), 6.79 (d, J = 3.3 Hz, 1H), 6.20-6.15 (m, 1H), 4.94 (a, 1H), 4.83 (a, 1H), 4.45 (s, 2H), 3.32 (d, J = 6.9 Hz, 2H), 2.84 (t, J = 7.4 Hz, 2H), 2.78 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 2.13 (s, 3H), 2.10-1.90 (m, 2H), 1.55 -1.40 (m, 1H), 0.90-0.70 (m, 6H).

Ejemplo de Referencia 5 Solución de metil t-butil éter en cloruro de 4-metil-2-tiazolilsulfonilo Reference Example 5 Solution of methyl t-butyl ether in 4-methyl-2-thiazolylsulfonyl chloride

15 En una atmósfera de argón, a una solución de 4-metiltiazol (3,0 g) en metil t-butil éter (45 ml), se le añadió con agitación n-butil·litio (solución 1,58 M en hexano, 19,1 ml) a -78 ºC y la mezcla se agitó durante 1 hora. Se añadió gota a gota una solución 5,72 M de dióxido de azufre en tetrahidrofurano (5,3 ml) a la mezcla y la mezcla se agitó durante 1 hora. A la mezcla, se le añadió N-clorosuccinimida (4,44 g). Después, la mezcla se calentó a 0 ºC y se agitó durante 1 hora más. Se añadió agua a la mezcla de reacción y la fase orgánica se lavó dos veces con agua, una vez con una solución acuosa saturada de cloruro sódico y se secó sobre sulfato de magnesio anhidro para dar el compuesto del título, en forma de una solución de metil t-butil éter (92 ml). La concentración de esta solución fue 0,20 M. El rendimiento conversión del compuesto del título fue 3,69 g. In an argon atmosphere, to a solution of 4-methylthiazole (3.0 g) in methyl t-butyl ether (45 ml), n-butyl·litium (1.58 M solution in hexane, was added with stirring, 19.1 ml) at -78 ° C and the mixture was stirred for 1 hour. A 5.72 M solution of sulfur dioxide in tetrahydrofuran (5.3 ml) was added dropwise to the mixture and the mixture was stirred for 1 hour. To the mixture, N-chlorosuccinimide (4.44 g) was added. Then, the mixture was heated to 0 ° C and stirred for an additional hour. Water was added to the reaction mixture and the organic phase was washed twice with water, once with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate to give the title compound, as a solution of methyl t-butyl ether (92 ml). The concentration of this solution was 0.20 M. The conversion yield of the title compound was 3.69 g.

25 Ejemplo 8 1-(4-Metiltiazol-2-ilsulfoniloxi)-1,2,3-benzotriazol Example 8 1- (4-Methylthiazol-2-ylsulfonyloxy) -1,2,3-benzotriazole

En una atmósfera de argón, a una solución de cloruro de 4-metiltiazol-2-sulfonilo en metil t-butil éter (0,20 M, 20 ml), se le añadieron con agitación 1-hidroxibenzotriazol (549 mg) y trietilamina (0,57 ml) con refrigeración en un baño de hielo y la mezcla se agitó durante 1 hora a temperatura ambiente. A la mezcla de reacción, se le añadió acetato de etilo se añadió. La fase orgánica se lavó sucesivamente tres veces con agua, una vez con una solución saturada acuosa de cloruro sódico, se secó sobre sulfato de magnesio anhidro y se concentró para dar el compuesto de la Under an argon atmosphere, a solution of 1-hydroxybenzotriazole (549 mg) and triethylamine (549 mg) and triethylamine were added with stirring to 4-methylthiazol-2-sulfonyl chloride in methyl t-butyl ether (0.20 M, 20 ml). 0.57 ml) with cooling in an ice bath and the mixture was stirred for 1 hour at room temperature. To the reaction mixture, ethyl acetate was added. The organic phase was washed successively three times with water, once with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated to give the compound of the

35 presente invención (1,1 g) que tenía los siguientes datos físicos. RMN: δ 8,03 (dt, J = 8,4, 1,0 Hz, 1H), 7,70-6,57 (m, 2H), 7,53 (d, J = 1,0 Hz, 1H), 7,46 (ddd, J = 8,4, 5,8, 2,0 Hz, 1H), 2,62 (d, J = 1,0 Hz, 3H). The present invention (1.1 g) which had the following physical data. NMR: δ 8.03 (dt, J = 8.4, 1.0 Hz, 1H), 7.70-6.57 (m, 2H), 7.53 (d, J = 1.0 Hz, 1H ), 7.46 (ddd, J = 8.4, 5.8, 2.0 Hz, 1H), 2.62 (d, J = 1.0 Hz, 3H).

Ejemplo 9 Sal cloruro de hidrógeno de 1-(4-metiltiazol-2-ilsulfonil)-3-metilimidazol-1-onio Example 9 1- (4-Methylthiazol-2-ylsulfonyl) -3-methylimidazol-1-onium hydrogen chloride salt

En una atmósfera de argón, se enfrió una solución de cloruro de 4-metiltiazol-2-sulfonilo en metil t-butil éter (0,14 M, Under an argon atmosphere, a solution of 4-methylthiazol-2-sulfonyl chloride in methyl t-butyl ether (0.14 M,

45 30 ml) a 0 ºC, después, se añadió 1 -metilimidazol (0,68 ml) y la mezcla se agitó durante 1 hora. El precipitado de color blanco aparecido se recogió y se secó para dar el compuesto de la presente invención (1,56 g) que tenía los siguientes datos físicos. RMN (DMSOd6): δ 9,08 (s a, 1H), 7,69 (t, J = 1,8 Hz, 1H), 7,63 (t, J = 1,8 Hz, 1H), 7,20-7,17 (m, 1H), 3,96 (s, 3H), 2,31 (d, J = 1,8 Hz, 3H). 45 ml) at 0 ° C, then 1-methylimidazole (0.68 ml) was added and the mixture was stirred for 1 hour. The white precipitate appeared was collected and dried to give the compound of the present invention (1.56 g) having the following physical data. NMR (DMSOd6): δ 9.08 (sa, 1H), 7.69 (t, J = 1.8 Hz, 1H), 7.63 (t, J = 1.8 Hz, 1H), 7.20 -7.17 (m, 1H), 3.96 (s, 3H), 2.31 (d, J = 1.8 Hz, 3H).

Entre los compuestos de fórmula (I) de la presente invención, los compuestos en los que Ar es tiazol (preparado en los Ejemplos 2(42) a (45), (47), (48), (50) a (60), (63) a (74), (101) y (103) a (123), Ejemplos 3(10) ,(11), (14) a (20), Ejemplos 4(10), (11), (13) a (16), Ejemplos 5(5) a (9), (22) a (26), (31) a (33), (40) a (43), (50), (52), (56), (57), (59), (60), (62), (63), Ejemplo 6, Ejemplos 6(4), (5), (8) a (10)), los compuestos en los que Ar es piridina (preparados en los Ejemplos 2(75) a (97), Ejemplos 3(21) a (38), Ejemplos 4(18) a (22)) pueden prepararse por los mismos procedimiento que el Ejemplo de Referencia 3, usando los compuestos preparados en los Ejemplos 8 y 9 o un compuesto correspondiente en lugar de un cloruro de sulfonilo correspondiente, seguido de los procedimientos correspondiente. Among the compounds of formula (I) of the present invention, the compounds in which Ar is thiazole (prepared in Examples 2 (42) to (45), (47), (48), (50) to (60) , (63) to (74), (101) and (103) to (123), Examples 3 (10), (11), (14) to (20), Examples 4 (10), (11), ( 13) to (16), Examples 5 (5) to (9), (22) to (26), (31) to (33), (40) to (43), (50), (52), ( 56), (57), (59), (60), (62), (63), Example 6, Examples 6 (4), (5), (8) to (10)), the compounds in which Ar is pyridine (prepared in Examples 2 (75) to (97), Examples 3 (21) to (38), Examples 4 (18) to (22)) can be prepared by the same procedure as Reference Example 3, using the compounds prepared in Examples 8 and 9 or a corresponding compound instead of a corresponding sulfonyl chloride, followed by the corresponding procedures.

5 Ejemplo Comparativo 1 5 Comparative Example 1

Una comparación de la estabilidad de cloruro de 4-metil-2-tiazolilsulfonilo con aquella del compuesto preparado en los Ejemplos 8 y 9 A comparison of the stability of 4-methyl-2-thiazolylsulfonyl chloride with that of the compound prepared in Examples 8 and 9

10 La solución preparada en Ejemplo de Referencia 1 se concentró a presión reducida para dar cloruro de 4-metil-2tiazolilsulfonilo. La estabilidad de este compuesto y los compuestos preparados en los Ejemplos 8 y 9 se midió por HPLC. Las condiciones de HPLC fueron como se indica a continuación. The solution prepared in Reference Example 1 was concentrated under reduced pressure to give 4-methyl-2-thiazolylsulfonyl chloride. The stability of this compound and the compounds prepared in Examples 8 and 9 was measured by HPLC. The HPLC conditions were as indicated below.

15 Columna: YMC-Pack ODS-AM-302(4,6 mm * 150 mm) Disolvente de elusión: MeCN/fosfato de tetra-n-butilamonio 3 mM = 40/60 Caudal: 1 ml/min Detectado mediante UVabs 220 nm 15 Column: YMC-Pack ODS-AM-302 (4.6 mm * 150 mm) Elution solvent: MeCN / 3 mM tetra-n-butylammonium phosphate = 40/60 Flow rate: 1 ml / min Detected by UVabs 220 nm

20 Los resultados se muestran en la Tabla 4. 20 The results are shown in Table 4.

Compuestos Compounds: Temperatura (ºC) Tiempo (horas) Tasa Residual (%) Temperature (ºC) Time (hours) Residual Rate (%)

1 one: 24 102,0 24 102.0

1 one: 48 96,3 48 96.3

1 one: 72 98,6 72 98.6

Cloruro de 4-metil-2-tiazolilsulfonilo 4-methyl-2-thiazolylsulfonyl chloride: 20 24 71,4 twenty 24 71.4

20 twenty: 48 20,6 48 20.6

20 twenty: 66 2,0 66 2.0

40 40: 16 60,9 16 60.9

40 40: 24 7,6 24 7.6

Compuesto preparado en el Ej. 8 Compound prepared in Ex. 8: 40 24 99,8 40 24 99.8

Compuesto preparada en el Ej. 9 Compound prepared in Ex. 9: 40 24 99,6 40 24 99.6

La Tabla 4 muestra que el cloruro de 4-metil-2-tiazolilsulfonilo es estable a baja temperatura, pero cuando se somete a temperatura ambiente o superior, es difícil asegurar la estabilidad. Table 4 shows that 4-methyl-2-thiazolylsulfonyl chloride is stable at low temperature, but when subjected to room temperature or higher, it is difficult to ensure stability.

25 Por otro lado, los compuestos preparados en los Ejemplos 8 y 9 son estables incluso a altas temperaturas, puesto que la tasa residual de los mismos apenas cambió cuando se dejaron a 40 ºC durante un día. On the other hand, the compounds prepared in Examples 8 and 9 are stable even at high temperatures, since the residual rate thereof hardly changed when they were left at 40 ° C for one day.

Por lo tanto, el compuesto de fórmula (II), dado en la presente invención, es útil como un intermedio para un 30 compuesto de sulfonamida, puesto que su estabilidad está mejorada en comparación con el compuesto de haluro de sulfonilo correspondiente. Therefore, the compound of formula (II), given in the present invention, is useful as an intermediate for a sulfonamide compound, since its stability is improved compared to the corresponding sulfonyl halide compound.

Ejemplo de Formulación 1: Formulation Example 1:

35 Los siguientes compuestos se mezclaron en un método convencional y se prensaron para obtener 100 comprimidos que contenían, cada uno, 5 mg de ingrediente activo. The following compounds were mixed in a conventional method and pressed to obtain 100 tablets each containing 5 mg of active ingredient.

• ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 500 mg • 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid 500 mg

• Glicolato cálcico de celulosa (disgregante) 200 mg 40 • Estearato de magnesio (lubricante) 100 mg • Cellulose calcium glycolate (disintegrant) 200 mg 40 • Magnesium stearate (lubricant) 100 mg

• Celulosa microcristalina 9,2 g • 9.2 g microcrystalline cellulose

Ejemplo de Formulación 2: Formulation Example 2:

45 Los siguientes compuestos se mezclaron en un método convencional y la solución se esterilizó, se introdujo en viales que contenían, cada uno, 1 ml y se liofilizó para obtener 100 viales que contenían, cada uno, 5 mg de ingrediente activo. The following compounds were mixed in a conventional method and the solution was sterilized, placed in vials containing, each, 1 ml and lyophilized to obtain 100 vials containing, each, 5 mg of active ingredient.

• ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico 500 mg 50 • Mannit 50 g • 3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid 500 mg 50 • Mannit 50 g

• Agua destilada 100 ml • 100 ml distilled water

Claims

1. An N-phenylethylsulfonylamide compound of formula (I)

wherein R1 is COOH, 5-tetrazolyl, or 5-oxo-1,2,4-oxadiazolyl; R2 is hydrogen, methyl, methoxy or chlorine; R3 and R4 are a combination of (1) methyl and methyl, (2) methyl and chlorine, or (3) chlorine and methyl; or R3 and R4 are taken together with the carbon to which R3 and R4 are attached to form a cyclopentene, cyclohexene or benzene ring; R5 is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl; Ar is pyridyl, 5-methyl-2-furyl or thiazolyl optionally substituted with methyl; and n is zero or 1 and when R1 is 5-tetrazolyl or 5-oxo-1,2,4-oxadiazolyl, n is zero, an alkyl ester thereof or a non-toxic salt thereof, with the condition that 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid is excluded,

15 an alkyl ester thereof or a non-toxic salt thereof.

2. 2.: El compuesto de acuerdo con la reivindicación 1, en el que Ar es 5-metil-2-furilo, 2-tiazolilo, 5-metil-2-tiazolilo, 2piridilo o 3-piridilo. The compound according to claim 1, wherein Ar is 5-methyl-2-furyl, 2-thiazolyl, 5-methyl-2-thiazolyl, 2-pyridyl or 3-pyridyl.

3. 3.: El compuesto de acuerdo con la reivindicación 1, en el que Ar es 5-metil-2-furilo. The compound according to claim 1, wherein Ar is 5-methyl-2-furyl.

4. Four.: El compuesto de acuerdo con la reivindicación 1 ó 3, que se selecciona entre el grupo que consiste en The compound according to claim 1 or 3, which is selected from the group consisting of

(4) (4): Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,25 (5) Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, 4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid, 25 (5) 4- [2- [N-Isopropyl- N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(6) (6): Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(7) (7): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(8) (8): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(9) (9): Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(10) (10): Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Chloro-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(11) (eleven): Ácido 3-metoxi-9-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Methoxy-9- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(12) (12): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(13) (13): Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Methoxy-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(14) (14): Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,35 (15) Ácido 3-metoxi-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, 3-Methoxy-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid, 35 (15) 3-Methoxy-4- [2 - [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(16) (16): Ácido 3-cloro-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Chloro-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(17) (17): Ácido 3-cloro-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Chloro-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(18) (18): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid,

(19) (19): Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(20) (twenty): Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,4- [2- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(21) (twenty-one): Ácido 4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,4- [2- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(23) (2. 3): Ácido 3-metil-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(24) (24): Ácido 3-metil-4-[2-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-9,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -9,5-dimethylphenoxymethyl] cinnamic acid,

(25) (25): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,45 (26) Ácido 4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid, 45 (26) 4- [2- [N- isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic,

(27) (27): N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida,N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide,

(28) (28): Ácido 3-metoxi-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, 3-Methoxy-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(29) (29): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide,

(30) (30): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide,

(31) (31): N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide,

(32) (32): N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl ) sulfonylamide,

(33) (33): N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida,N- [4-Chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl ) sulfonylamide,

(34) (3. 4): Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(35) (35): Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,55 (36) Ácido 4-[7-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-1,2,3,4-tetrahidronaftalen-6-iloximetil]benzoico, 4- [6- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, 55 (36) 4- [7- [N-Isobutyl-N- ( 5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid,

(37) (37): Ácido 4-[7-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]-1,2, 3, 4-tetrahidronaftalen-6-iloximetil]benzoico, 4- [7- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] -1,2,3,4-tetrahydronaphthalen-6-yloxymethyl] benzoic acid,

(38) (38): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) ) sulfonylamide,

(39) (39): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,9-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,9-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl ) sulfonylamide,

(40) (40): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2-furil)sulfonilamida N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl) sulfonylamide

(41) (41): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide,

(42) (42): N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2-furil)sulfonilamida,N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl) sulfonylamide ,

(43) (43): Ácido 3-metil-4-[2-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico, 3-Methyl-4- [2- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(44) (44): N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(5-metil-2furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (5-methyl-2-furyl ) sulfonylamide,

(45) (Four. Five): N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(5-metil-2furil)sulfonilamida, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (5-methyl-2-furyl ) sulfonylamide,

(46) (46): Ácido 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(47) (47): Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(48) (48): Ácido 3-metil-4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(49) (49): Ácido 4-[2-[N-(2-metil-2-propenil)-N-(5-metil-2-furilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N- (2-methyl-2-propenyl) -N- (5-methyl-2-furylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(50) (fifty): Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(51) (51): Ácido 3-metil-4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(52) (52): Ácido 4-[6-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(53) (53): Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]-2-naftiloximetil]benzoico,4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] -2-naphthyloxymethyl] benzoic acid,

(55) (55): Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] benzoic acid,

(56) (56): Ácido 4-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico, 4- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid,

(57) (57): Alcohol 4-[6-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbencílico,4- [6- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzyl alcohol,

(59) (59): Ácido 4-[6-[N-etil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico,4- [6- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid,

(60) (60): Ácido 4-[6-[N-metil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-methyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(61) (61): Ácido 4-[6-[N-etil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(62) (62): Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-propilamino]indan-5-iloximetil]cinámico,4- [6- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid,

(63) (63): Ácido 4-[4,5-dimetil-2-[N-(2-metil-2-propenil)-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metil-benzoico,4- [4,5-Dimethyl-2- [N- (2-methyl-2-propenyl) -N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methyl-benzoic acid,

(64) (64): Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-metil-2-propenil)amino]indan-5-iloximetil]cinámico,4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-methyl-2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid,

(65) (65): Ácido 9-[6-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]cinámico,9- [6- [N-Cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(66) (66): Ácido 4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]cinámico,4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid,

(67) (67): Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-propilamino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid,

(68) (68): Ácido 3-metil-4-[6-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid,

(70) (70): Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]benzoico,4- [4,5-Dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] benzoic acid,

(71) (71): Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-propilaminolfenoximetil]benzoico,4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N-propylaminolfenoxymethyl] benzoic acid,

(72) (72): Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico,4- [3- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(73) (73): Ácido 4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico,4- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(74) (74): Ácido 4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico,4- [3- [N-Isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(75) (75): Ácido 9-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico,9- [3- [N-Isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(76) (76): Ácido 3-metil-4-[3-[N-isopropil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico,3-Methyl-4- [3- [N-isopropyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(77) (77): Ácido 3-metil-4-[3-[N-isobutil-N-(5-metil-2-furilsulfonil)amino]naftalen-2-iloximetil]cinámico,3-Methyl-4- [3- [N-isobutyl-N- (5-methyl-2-furylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(78) (78): Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]fenoximetil]benzoico,4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] benzoic acid,

(80)(80): Ácido 4-[4,5-dimetil-2-[N-etil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metilbenzoico, 4- [4,5-Dimethyl-2- [N-ethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(81) (81): Ácido 9-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-propilamino]fenoximetil]-3-metilbenzoico,9- [4,5-dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N-propylamino] phenoxymethyl] -3-methylbenzoic acid,

(82) (82): Ácido 4-[4,5-dimetil-2-[N-(5-metil-2-furilsulfonil)-N-(2-propenil)amino]fenoximetil]-3-metilbenzoico,4- [4,5-Dimethyl-2- [N- (5-methyl-2-furylsulfonyl) -N- (2-propenyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(83) (83): Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsofonil)amino]fenoximetil]-3-metilbenzoico,4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsophonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(84) (84): Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsulfonil)amino]indan-5-iloximetil]-3-metilbenzoico,4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsulfonyl) amino] indan-5-yloxymethyl] -3-methylbenzoic acid,

(85) (85): Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(5-metil-2-furilsofonil)amino]fenoximetil]benzoico,4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (5-methyl-2-furylsophonyl) amino] phenoxymethyl] benzoic acid,

(86) (86): Ácido 4-[4,5-dimetil-2-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsofonil)amino]fenoximetil]benzoico,4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsophonyl) amino] phenoxymethyl] benzoic acid,

(87) (87): Ácido 4-[6-[N-(2-hidroxi-2-metilpropil)-N-(5-metil-2-furilsofonil)amino]indan-5-iloximetil]cinámico y4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (5-methyl-2-furylsophonyl) amino] indan-5-yloxymethyl] cinnamic acid and

(88) (88): Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(5-metil-2-furilsulfonil)amino]fenoximetil]-3-metilbenzoico. 4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (5-methyl-2-furylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid.

5. 5.: El compuesto de acuerdo con la reivindicación 1, en el que Ar es 2-tiazolilo o 5-metil-2-tiazolilo. The compound according to claim 1, wherein Ar is 2-thiazolyl or 5-methyl-2-thiazolyl.

6. 6.: El compuesto de acuerdo con la reivindicación 1 ó 5, que se selecciona entre el grupo que consiste en The compound according to claim 1 or 5, which is selected from the group consisting of

(7)(7): Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico, 4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(12) (12): Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(13) (13): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(14) (14): Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(16) (16): Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(17) (17): Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-9-cloro-5-metilfenoximetil]benzoico,3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -9-chloro-5-methylphenoxymethyl] benzoic acid,

(22) (22): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(23) (2. 3): Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(24) (24): Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(26) (26): Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(27) (27): Ácido 3-metil-9-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-9- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(28) (28): Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(29) (29): Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(30) (30): Ácido 3-cloro-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico, 3-Chloro-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(31) (31): Ácido 4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(32) (32): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(33) (33): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico,4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid,

(36) (36): Ácido 3-metil-4-[2-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(37) (37): Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(38) (38): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(39) (39): Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(40) (40): Ácido 3-metil-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico, 3-Methyl-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid,

(41) (41): N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide,

(42) (42): N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida,N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide,

(43)(43): Ácido 4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, 4- [2- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(46) (46): Ácido 3-cloro-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, 3-Chloro-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(47) (47): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide,

(48) (48): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide,

(49) (49): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide,

(50) (fifty): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide,

(51) (51): N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide,

(52) (52): N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide,

(53) (53): N-[4-cloro-5-metil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2tiazolil)sulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide ,

(54) (54): N-[4-cloro-5-metil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2tiazolil)sulfonilamida,N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl -2 thiazolyl) sulfonylamide,

(55) (55): Ácido 3-metoxi-4-[2-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, 3-Methoxy-4- [2- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(56) (56): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) ) sulfonylamide,

(57) (57): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) ) sulfonylamide,

(58) (58): N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide ,

(59)(59): N-[4,5-dimetil-2-[4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-(4-metil-2-tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl- (4-methyl-2-thiazolyl) sulfonylamide ,

(60) (60): N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2tiazolil)sulfonilamida, N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) ) sulfonylamide,

(61) (61): N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-(4-metil-2-tiazolil)sulfonilamida,N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl- (4-methyl-2-thiazolyl) sulfonylamide,

(62) (62): Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(63) (63): Ácido 4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(64) (64): Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(65) (65): Ácido 3-metil-4-[6-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(66) (66): Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4-cloro-5metilfenoximetil]benzoico,3-methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(68) (68): Ácido 3-metil-4-[2-[N-(2-metil-2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Methyl-4- [2- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(69) (69): Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(71) (71): Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,3-methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(72) (72): Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(73) (73): Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(74) (74): Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico,4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(75) (75): Ácido 4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(76) (76): Ácido 3-metil-4-[6-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(77) (77): Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(78) (78): Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(79) (79): Ácido 4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,4- [2- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(80) (80): Ácido 4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,4- [2- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(81) (81): Ácido 4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(82) (82): Ácido 4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,4- [6- [N-Isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(83) (83): Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(84) (84): Ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(85) (85): Ácido 3-metil-4-[2-[N-isopropil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(86) (86): Ácido 3-metil-4-[2-[N-isobutil-N-(2-tiazolilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(87) (87): Ácido 3-metil-4-[6-[N-isopropil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isopropyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(88) (88): Ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]cinámico,3-Methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid,

(89) (89): Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico,4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid,

(90) (90): Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]benzoico,4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] benzoic acid,

(91) (91): Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]-3-metilbenzoico,4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(92) (92): Ácido 4-[3-[N-isopropil-N-[2-(4-metiltiazolil)sulfonil]amino]naftalen-2-iloximetil]-3-metilbenzoico,4- [3- [N-Isopropyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(93) (93): Ácido 4-[3-[N-isobutil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico,4- [3- [N-Isobutyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(94) (94): Ácido 4-[3-[N-isopropil-N-(4-metil-2-tiazolilsulfonil)amino]naftalen-2-iloximetil]cinámico,4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] cinnamic acid,

(96) (96): Ácido 4-[4,5-dimetil-2-[N-etil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico,4- [4,5-Dimethyl-2- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(97) (97): Ácido 4-[4,5-dimetil-2-[N-propil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico, 4- [4,5-dimethyl-2- [N-propyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(98) (98): Ácido 4-[4,5-dimetil-2-[N-(2-propenil)-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico,4- [4,5-dimethyl-2- [N- (2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(99) (99): Ácido 4-[4,5-dimetil-2-[N-ciclopropilmetil-N-(4-metil-2-tiazolilsulfonil)amino]fenoximetil]-3-metilbenzoico,4- [4,5-Dimethyl-2- [N-cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(100) 4- [4,5-Dimethyl-2- [N- (2-hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] phenoxymethyl] -3-methylbenzoic acid,

(101) 4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(102) 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] benzoic acid,

(103) 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(104) 4- [3- [N-Isobutyl-N- [2- (4-methylthiazolyl) sulfonyl] amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(105) 4- [3- [N-Isopropyl-N- (4-methyl-2-thiazolylsulfonyl) amino] naphthalen-2-yloxymethyl] -3-methylbenzoic acid,

(106) 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid,

(107) 4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] benzoic acid,

(110) 4- [6- [N-ethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid,

(111) 3-Methyl-4- [6- [N- (2-methyl-2-propenyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] cinnamic acid, (111)

(112) 4- [6- [N-Cyclopropylmethyl-N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid,

(113) 3-Methyl-4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N- (2-propenyl) amino] indan-5-yloxymethyl] cinnamic acid,

(114) 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] -3-methylcinamic acid,

(115) 3-Methyl-4- [6- [N- (4-methyl-2-thiazolylsulfonyl) -N-propylamino] indan-5-yloxymethyl] cinnamic acid and

(116) 4- [6- [N- (2-Hydroxy-2-methylpropyl) -N- (4-methyl-2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid.

7. 7.: El compuesto de acuerdo con la reivindicación 1, en el que Ar es 2-piridilo o 3-piridilo. The compound according to claim 1, wherein Ar is 2-pyridyl or 3-pyridyl.

8. 8.: El compuesto de acuerdo con la reivindicación 1 ó 7, que se selecciona entre el grupo que consiste en The compound according to claim 1 or 7, which is selected from the group consisting of

(3) (3): Ácido 3-cloro-4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-Chloro-4- [2- [N-isopropyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(4) (4): Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(5) (5): Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] benzoic acid,

(6) (6): Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(9) (9): Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(10) (10): Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(12) (12): Ácido 3-metoxi-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Methoxy-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(13) (13): Ácido 3-metoxi-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-Methoxy-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(14) (14): Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(15) (fifteen): Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(18) (18): Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]benzoico,3-methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] benzoic acid,

(19) (19): Ácido 4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]benzoico,4- [2- [N-Isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] benzoic acid,

(21) (twenty-one): Ácido 4-[2-[N-isopropil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,4- [2- [N-Isopropyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(22) (22): Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4-metil-5-clorofenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4-methyl-5-chlorophenoxymethyl] cinnamic acid,

(23) (2. 3): Ácido 3-metil-4-[2-[N-isobutil-N-(2-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (2-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(24) (24): Ácido 4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,4- [2- [N-Isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(25) (25): Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico,3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(27) (27): Ácido 3-cloro-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4,5-dimetilfenoximetil]cinámico, 3-Chloro-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4,5-dimethylphenoxymethyl] cinnamic acid,

(28) (28): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide,

(29) (29): N-[4,5-dimetil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide,

(30) (30): N-[4-cloro-5-metil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N- [4-Chloro-5-methyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide,

(31) (31): N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide,

(32) (32): N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-3-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-3-pyridylsulfonylamide,

(33) (33): N-[4,5-dimetil-2-[2-cloro-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida;N- [4,5-dimethyl-2- [2-chloro-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide;

(34) (3. 4): Ácido 3-metil-4-[2-[N-isobutil-N-(3-piridilsulfonil)amino]-4-cloro-5-metilfenoximetil]cinámico, 3-Methyl-4- [2- [N-isobutyl-N- (3-pyridylsulfonyl) amino] -4-chloro-5-methylphenoxymethyl] cinnamic acid,

(35) (35): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide,

(36) (36): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide,

(37) (37): N-[4,5-dimetil-2-[4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N- [4,5-dimethyl-2- [4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide,

(39) (39): N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide,

(40) (40): N-[4-cloro-5-metil-2-[2-metil-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N- [4-Chloro-5-methyl-2- [2-methyl-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide,

(41) (41): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide,

(42) (42): N-[4,5-dimetil-2-[2-metil-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-3-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methyl-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl-3-pyridylsulfonylamide,

(43) (43): N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide,

(44) (44): N-[4,5-dimetil-2-[2-metoxi-4-(5-tetrazolil)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida, N- [4,5-dimethyl-2- [2-methoxy-4- (5-tetrazolyl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide,

(45) (Four. Five): N-[9,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isobutil-2-piridilsulfonilamida y N- [9,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isobutyl-2-pyridylsulfonylamide and

(46) (46): N-[4,5-dimetil-2-[2-metoxi-4-(5-oxo-1,2,4-oxadiazol-3-il)fenilmetiloxi]fenil]-N-isopropil-2-piridilsulfonilamida. N- [4,5-dimethyl-2- [2-methoxy-4- (5-oxo-1,2,4-oxadiazol-3-yl) phenylmethyloxy] phenyl] -N-isopropyl-2-pyridylsulfonylamide.

9. 9.: El compuesto de fórmula (I) de acuerdo con una cualquiera de las reivindicaciones 1 a 8, un éster alquílico del mismo o una sal no tóxica del mismo para uso como un antagonista del receptor EP1. The compound of formula (I) according to any one of claims 1 to 8, an alkyl ester thereof or a non-toxic salt thereof for use as an EP1 receptor antagonist.

10. 10.: Un compuesto que es ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5-iloximetil]benzoico, un éster alquílico del mismo o una sal no tóxica del mismo para uso como un antagonista del receptor EP1. A compound that is 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5-yloxymethyl] benzoic acid, an alkyl ester thereof or a non-toxic salt thereof for use as an EP1 receptor antagonist.

11.eleven.: El compuesto para uso de acuerdo con la reivindicación 9 ó 10, en el que la enfermedad que es susceptible de prevención y/o tratamiento por el antagonista del receptor EP1 es algia, pirexia (inducción de fiebre), polaquiuria (micción frecuente), acraturesis (incontinencia urinaria), síndrome de enfermedad del tracto urinario inferior o cáncer. The compound for use according to claim 9 or 10, wherein the disease that is susceptible to prevention and / or treatment by the EP1 receptor antagonist is algia, pyrexia (fever induction), polaquiuria (frequent urination), acraturesis (urinary incontinence), lower urinary tract disease syndrome or cancer.

12. 12.: Una composición farmacéutica, que comprende el compuesto de fórmula (I) de acuerdo con una cualquiera de las reivindicaciones 1 a 8, un éster alquílico del mismo o una sal no tóxica del mismo como ingrediente activo. A pharmaceutical composition, comprising the compound of formula (I) according to any one of claims 1 to 8, an alkyl ester thereof or a non-toxic salt thereof as an active ingredient.

13.13.: Una composición farmacéutica que comprende ácido 3-metil-4-[6-[N-isobutil-N-(2-tiazolilsulfonil)amino]indan-5iloximetil]benzoico, un éster alquílico del mismo o una sal no tóxica del mismo como ingrediente activo. A pharmaceutical composition comprising 3-methyl-4- [6- [N-isobutyl-N- (2-thiazolylsulfonyl) amino] indan-5yloxymethyl] benzoic acid, an alkyl ester thereof or a non-toxic salt thereof as active ingredient .