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WO1996016038A1 - Derive de 2-[2-(indol-3-yl)ethylamino]-1-phenylethanol - Google Patents

Derive de 2-[2-(indol-3-yl)ethylamino]-1-phenylethanol Download PDF

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Publication number
WO1996016038A1
WO1996016038A1 PCT/JP1994/001941 JP9401941W WO9616038A1 WO 1996016038 A1 WO1996016038 A1 WO 1996016038A1 JP 9401941 W JP9401941 W JP 9401941W WO 9616038 A1 WO9616038 A1 WO 9616038A1
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formula
atom
group
compound
hydrogen atom
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PCT/JP1994/001941
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English (en)
Japanese (ja)
Inventor
Shiro Kato
Hiroshi Harada
Toshiya Morie
Yoshimi Hirokawa
Naoyuki Yoshida
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Dainippon Pharmaceutical Co., Ltd.
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Priority to PCT/JP1994/001941 priority Critical patent/WO1996016038A1/fr
Priority to AU10341/95A priority patent/AU1034195A/en
Publication of WO1996016038A1 publication Critical patent/WO1996016038A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C07D209/16—Tryptamines

Definitions

  • the present invention 5 3 A Dorenari emissions receptor highly selective, 3 A Dorenarin novel 2 having a receptor stimulating effect [2- (Indoru one 3-I le) Echirua amino] one 1 one-phenylalanine ethanol Related to derivatives.
  • 3 adrenergic receptors have been isolated as a third subtype different from the two subtypes described above [E morine. L. J. et al .: Science, 5, 1118-1121 (1989). ]. These 3- adrenergic receptors are present in the digestive tract, adipose tissue and skeletal muscle, and are thought to be involved in energy consumption based on lipolysis, promotion of glycogen degradation, and relaxation of intestinal smooth muscle. 3 3 as a drug which selectively actuated adrenergic phosphorus receptors, e.g. SR- 5 8 6 1 1 A [(R S.) -.
  • 11A has an excellent inhibitory effect on spontaneous movement of the isolated rat colon.CBrit. J. Pharmacol., 100, 831-839 (1990)]
  • an indole derivative represented by the following formula (VI) and a pharmaceutically acceptable non-toxic acid addition salt thereof have a bronchodilator effect and a central nervous system. It is disclosed to show valuable effects on the system (antiemetic and hypnotic enhancing effects).
  • This specification mentions 3- [2- [2-hydroxy-2- (3.4-dihydroxyphenyl) ethylamino] propyl] indole as the most preferred compound.
  • Alk represents a straight-chain or branched-chain alkylene group having 2 to 4 carbon atoms
  • X represents a hydrogen atom or a hydroxyl group
  • Y represents a hydroxyl group or a methoxy group.
  • R represents a phenyl group, an m-ditrophenyl group or a p-ditrophenyl group, and R 1 represents a hydrogen atom or a methyl group.
  • An object of the present invention is to provide a 2- [2- (indole-13-yl) ethylamino] 1-1-phenyl having an excellent ⁇ 3- adrenergic receptor stimulating effect having a chemical structure different from that of a conventional known compound.
  • Provided are an ethanol derivative and an acid addition salt thereof, and a method for producing the ethanol derivative and an acid addition salt thereof. Is to provide the law.
  • a 2- [2- (indole-13-yl) ethylamino] -11-phenylethanol derivative represented by the following formula (I) and a pharmaceutically acceptable acid addition salt thereof are provided.
  • R 2 represents a hydrogen atom, a lower alkyl group or a fluoro lower alkyl group
  • R 3 represents a hydrogen atom, a halogen atom, a trifluoromethyl group, a nitro group or a cyano group.
  • Examples of the pharmaceutically acceptable acid addition salt of the compound represented by the formula (I) include inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate and the like. Salts and organic acid salts such as oxalate, maleate, fumarate, lactate, malate, citrate, tartrate, benzoate and methanesulfonate. Since the compound represented by the formula (I) and a pharmaceutically acceptable acid addition salt thereof may exist in the form of a hydrate or a solvate, these hydrates and solvates may also be used. Included in the compounds of the present invention.
  • the compound represented by the formula (I) has at least one asymmetric carbon violet atom, that is, a carbon atom to which a hydroxy group is bonded in the formula (I). Further, when R 2 is a lower alkyl group or a fluoro lower alkyl group, the carbon atom to which this group is bonded is also an asymmetric carbon atom. Therefore, equation (I) In the formula, when R 2 is a hydrogen atom, there may be two kinds of stereoisomers, and when R 2 is a lower alkyl group or a fluoro lower alkyl group, there may be four kinds of stereoisomers. These stereoisomers, their mixtures and racemates are included in the compounds of the present invention.
  • lower alkyl group means one having 1 to 3 carbon atoms, and includes methyl, ethyl, propyl and isopropyl, with methyl being particularly preferred.
  • “Fluoro-lower alkyl group” refers to an alkyl group having 1 to 3 carbon atoms in which a hydrogen atom has been replaced with a fluorine atom, and examples thereof include fluoromethyl, trifluoromethyl, and 2-fluoroethyl. Particularly preferred.
  • Halogen atom means fluorine, chlorine, odor violet, and iodine violet, but fluorine, chlorine, and bromine are preferable, and fluorine and chlorine are particularly preferable.
  • the bonding position of R 3 may be any of the 4, 5, and 6.7 positions of the indole ring, but the 6 position is particularly preferred.
  • R 2 is a hydrogen atom or a methyl group
  • Ku R 3 is Wakashi fluorine atoms of the hydrogen atom or 6-position is a chlorine atom
  • Particularly preferred compounds are those wherein R 1 is a chlorine atom, R 2 is a methyl group and R 3 is a water atom or a fluorine atom or a chlorine atom at the 6-position in the formula (I), Is an acid addition salt that is acceptable.
  • the compound represented by R 2 or a group other than a hydrogen atom has two asymmetric groups. Since it has carbon atoms, there are four stereoisomers, but the (R, R) configuration is preferred.
  • Particularly preferred compounds include, for example, the following compounds and pharmaceutically acceptable acid addition salts thereof.
  • the compound of the present invention can be produced, for example, by the following method.
  • the reaction between the compound represented by the formula ( ⁇ ) and the compound represented by the formula (m) is carried out in a suitable solvent or without a solvent.
  • the three solvents to be used should be appropriately selected according to the type of the raw material compounds, etc., for example, alcohols such as methanol, ethanol, isopropyl alcohol, ketones such as acetone, methylethylketone, methylene chloride, Halogenated hydrocarbons such as black form, ethers such as dimethyl ether, tetrahydrofuran, dioxane, aromatic hydrocarbons such as benzene and toluene, ethyl acetate, N, N-dimethylform Amides, dimethyl sulfoxide and the like can be mentioned, and these solvents are used alone or in combination of two or more.
  • the compound of the formula (m) can be used in the form of an acid addition salt.
  • these acid addition salts include inorganic acid salts such as hydrochloride and hydrobromide, oxalate, and maleic acid.
  • Organic acid salts such as acid salts and fumarate salts.
  • the reaction is carried out in the presence of a base, and specific examples of the base include sodium bicarbonate, alkali bicarbonate such as potassium bicarbonate, sodium carbonate, and the like.
  • Carbonic acid such as sulfuric acid or triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine
  • the reaction temperature varies depending on the type of the starting compound used and the like, but is usually about 20 ° C to about 150 ° C, preferably about 25 ° C to about 100 ° C.
  • a compound of formula ([pi) are racemic compounds of formula (I) is a racemate obtained from compounds of formula R 2 is a hydrogen atom (m), R 2 is other than hydrogen atoms
  • the compound of formula (m) which is a group gives the compound of formula (I) which is a diastereomer mixture.
  • the enantiomer of the compound of the formula ( ⁇ ) can be obtained, for example, by the method of Bloom, JD et al. [J. Med. Chem., 3 ⁇ , 3081-3084 (1992)] or the method of Eliel, EL and Delmonte, DW [J. Org. Chem., 21. 596-597 (1956)].
  • the enantiomer of a compound in which R 2 is a group other than a hydrogen atom in the above formula ( ⁇ ) can be obtained, for example, by the method of Repke, DB and Ferguson, WJ [J. Heterocycl. Chem., 13, 775-778 (1976)] It can be manufactured according to.
  • R 2 means the same as described above, and R 3 means a hydrogen atom, a halogen atom or a trifluoromethyl group.
  • under normal conditions means conditions under the presence of a reducing agent capable of reducing the imine moiety without affecting the liponyl group or under the conditions of contact under normal conditions.
  • Examples of the reducing agent that can pass through the imine moiety without affecting the carbonyl group include, for example, sodium cyanoborohydride.
  • This reaction is carried out in an appropriate solvent, and suitable solvents include alcohols such as methanol and ethanol.
  • suitable solvents include alcohols such as methanol and ethanol.
  • the reaction temperature is usually about 20 ° C to about 80 ° C.
  • the product After producing the compound represented by the formula, the product can also be reduced to reduce the product.
  • the step of producing the compound of the formula (X) is carried out in a suitable solvent, and p-toluenesulfonic acid, pyridin p-toluenesulfonic acid and the like are used as the acid.
  • the solvent aromatic hydrocarbons such as benzene and toluene are preferable, and the reaction temperature is usually about 80 ° C to about 150 ° C.
  • the step of passing the compound of the formula (X) is performed under conditions suitable for the transfer of the imine moiety, and the reduction during the reaction between the compound of the formula (W) and the compound of the formula (V) is performed. The conditions can be adopted as they are.
  • This reduction step is also suitably performed using sodium borohydride as a base agent.
  • Preferred solvents include alcohols such as methanol and ethanol, and the reaction temperature is usually about It is from 10 ° C to about 25 ° C.
  • the main reaction is carried out in an ether solvent such as diethyl ether, tetrahydrofuran, dimethoxetane, dioxane, diglyme, and the reaction temperature varies depending on the type of the reducing agent, and is generally about 0 to about 0. One hundred sixty.
  • the starting compound represented by the formula (VI) is a novel substance, for example, the following formula (XI)
  • the reaction between the compound of the formula (XI) and the compound of the formula (SO) is carried out by the reaction of benzotriazole-N-oxytris (dimethylamino) phosphoniumhexafluorophosphate, dicyclohexylcarbodiimide, 1-ethyl-3- (3-di
  • a condensing agent such as methylaminopropyl) carbodiimide hydrochloride, N, N'-carbodilimidazole, 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline.
  • the reaction is carried out in an appropriate solvent, and the solvent used may be the same as the specific examples described in the production method (a), and the compound of the formula () may be the same as that described in the production method (a).
  • the reaction temperature is usually about 20 ° C to about 50 ° C.
  • the enantiomer of the compound in which R 2 is a group other than a hydrogen atom in the above formula ( ⁇ ) can be produced, for example, according to the method described in JP-A-63-225 ⁇ 9. can do.
  • the product obtained by each of the above production methods can be isolated and purified by a conventional method such as chromatography, recrystallization, and reprecipitation.
  • the product obtained by each of the above processes is in the form of an acid addition salt or a free base depending on the reaction conditions. These products can be converted into the desired acid addition salts or free bases by conventional methods.
  • each stereoisomer can be obtained by a conventional method, for example, a method described in European Patent Application Publication No. 455006. Can be separated.
  • Test Example 1 was performed in comparison with an existing adrenergic receptor agonist.
  • the existing 3 Adorenari emissions receptor agonist was used salbutamol as non-selective agonists as (1) one isoproterenol no le or [delta] 2 selective agonist.
  • Test Examples 1 to 3 were performed in accordance with the method of Bianchetti, A. and Manara, L. [Brit. J. Pharma col., 100. 831-839 (1990)].
  • Rat ⁇ 3 adrenergic receptor stimulating action Suppressive action on spontaneous contraction of the isolated rat colon:
  • the proximal colon was excised from an SD male rat weighing 350-400 g, and a 2.5-3 cm long specimen was prepared.
  • the specimen was Krebs-Henseleit (118 mM NaCl, 4.75 mM NaCl, 4.75 mM KC1.2.5 mM containing pentramin (10 M), desmethylimibramine (0.5 M) and hydrocortisone (30 / M).
  • CaCl 2. 1.2mM KH 2 P0 4 . 1.2mM MgS 0 4. 25mM NaHC0 3. 10 mM glucose) was filled with Ma Appended to Gunusu tube (1 Om 1) in 95% 0 2 - and kept at a mixed gas of 5% C0 2 through the gas while 37 hands.
  • Rat S 2 adrenergic receptor stimulating effect Suppressive effect on spontaneous contraction of the isolated rat uterus:
  • the uterus was excised from a non-pregnant Wistar female rat and a specimen was prepared by a conventional method. Specimens, full We Roh carboxymethyl mouth click containing benzal Min (12 ⁇ M) (Locke:. 15 7mM NaCl 5.6mM KC1, 2.2mM CaCl 2, 18mM NaH C0 3, 5.6mM glucose) Magnus tube filled with liquid (20 m 1) was vertical suspended in 95% 0 2 - 5% C0 2 c resting tension lg of the mixed gas was kept in aeration 37 ° C for loaded, after spontaneous contraction was stabilized, the test compound Cumulatively Was added.
  • benzal Min 12 ⁇ M
  • Magnus tube filled with liquid (20 m 1) was vertical suspended in 95% 0 2 - 5% C0 2 c resting tension lg of the mixed gas was kept in aeration 37 ° C for loaded, after spontaneous contraction was stabilized, the test compound Cumulatively Was added.
  • An isolated right atrial specimen with a pacemaker was prepared from a dd ⁇ ⁇ male guinea pig by a conventional method.
  • Specimens, modified click Repusu containing full Nokishibenzamin (12 iM) (Krebs:. 122.2mM NaCl, 4.2mM KC1, 2.5mM Ca Cl 2, ImM MgCl 2, 1.2mM NaH 2 P0 4, 15.5mM NaHC0 3 11.5mM Glucose ) was suspended in Magnus tube (20 m 1 in :) filled with 95% 0 2 - was incubated at 37 ° C for while passing 5% C0 2 gas mixture. A resting tension lg was applied and after 30 minutes the test compound was added cumulatively. 100% up ⁇ the right atrium rhythm number by the test compound was calculated by the least squares method concentrations showing the 50% (EC 50 value) from the dose first working curve.
  • Test compounds were orally administered to 18-hour fasted mice (7 to 11 mice per group). One hour later, 0.2 ml of a 5% charcoal powder suspension suspended in a 10% aqueous solution of gum arabic was orally administered per mouse, and 20 minutes later, the gastrointestinal tract was removed. The transfer rate of the tip of the charcoal powder to the entire small intestine was calculated. The compound of Example 2 showed a significant inhibitory effect on charcoal powder transport at a dose of lmg / kg.
  • Expression vector pKCRH2 for animal cells was digested with the restriction enzyme SalI and blunt-ended with a DNA Blunting Kit (Takara Shuzo).
  • another expression vector pS V2-neo for animal cells was digested with restriction enzymes Accl and Aatl I, and DNA Blunting was performed. The tip was made blunt by Kit.
  • This plasmid DNA was designated as pKCNO.
  • This plasmid pKCNO was digested with the restriction enzyme Hindi II, and ligated with the synthetic adapter 1 using the DNA Ligation Kit.
  • the sequence of Synthetic Adapter 1 is as follows. 5 * -AGCTCCTGCAGGCGCGCCGATATCTCGAGCGGCCGCGGTACCA-3 '
  • the sequences of oligonucleotides 1 and 2 are as follows.
  • coli HB101 by a conventional method, transformants were selected on LB agar medium containing ampicillin 100 / ml, and plasmid DNA was extracted from the transformants. Restriction As a result of examining the base sequence of a fragment of about 1.3 kbp obtained by digestion with enzymes Sse83871 and XhoI, this sequence was reported by Lelias et al. [FEB S Lett. 324: 127-130 (1994)]. The sequence was identical to that of the human drainage receptor cDNA. The plasmid DNA expressing the human drainage receptor was designated as pKREX10.
  • Human ⁇ 3 adrenergic receptor expression plasmid pKREX 10 was introduced into Chinese hamster ovary cells CHO—K1 (ATCC CCL 61) by calcium phosphate method, and the transformant was transformed to 600 ig / ml G—418. Selection was performed using MEM-Dulbecco medium (ICN Biomedicals) containing (Lif e Technologies). The medium was supplemented with 10% fetal calf serum and 11.5 g / ml proline.
  • the cells were detached by leaving them to stand at 37 ° C for 10 minutes in phosphate buffered saline containing 0.5 mM ethylenediaminetetraacetic acid (EDTA). Collect more cells to centrifugation and suspended at about 5 XLO e cells / m 1 in 10 mM Tris-HCl slow ⁇ (p H 7.5) containing ImM EDTA. This suspension was prepared by adding 201 11.5 nM (-) 3- [ 125I ] iodocyanopindolol (Amersham3 ⁇ 4: 1% serum albumin, 0.1% NaN 3 and 2 OmM HEPES buffer (pH 7.4).
  • EDTA ethylenediaminetetraacetic acid
  • test compound was mixed with this suspension 201 in RPMI-1640 medium 100 ⁇ 1 containing 1% serum albumin, 0.1% NaN 3 and 2 OmM HEPE S buffer (pH 7.4). Then, the mixture was allowed to stand for 30 minutes at 4, and then 0.2 nM (-) 3- [ 125I ] iodocyanopindolol 100 ⁇ 1 was added thereto, and the mixture was allowed to stand for further 4 hours.
  • the glass filter was pre-washed with a glass filter GF / C soaked in 0.3% polyethyleneimine in advance, and the radioactivity on the filter was measured using an X-ray detector.
  • the amount of binding with or without imM (—)-alprenolol was 100% inhibition and 0% inhibition, respectively.
  • the concentration that inhibits the binding amount by 50% is the minimum from the concentration-inhibition ratio curve. It was calculated by the square method. Table 2 shows the results.
  • the human 5 3 Adorenarin receptor withers expressing cell line CH O / pKREXl 0- 36 10% ⁇ shea fetal serum was prepared in the manner of, proline of 11.5 ⁇ g / m 1, and 200 g / m 1 of G — MEM containing 418 —
  • CHO / pKREXl O-36 is collected by the same method as in Test Example 5 and contains 1 mM ascorbic acid and 1 mM 3-isobutyl-1-methylxanthine
  • the cells were suspended in Hanks' balanced salt solution (ICN Biooraedicals) at about 2 ⁇ 10 6 cells / ml.
  • This suspension 1001 and the test compound were mixed in the same equilibrium salt solution 5001, and allowed to react at 37 ° C for 30 minutes, followed by boiling for 5 minutes to stop the reaction. After centrifuging the reaction solution, the amount of cyclic AMP in the supernatant was measured using the cAMP EIA System (Amershara). 10 - 5 M (-) Saikuri' of over I source when added to pro tele Knoll or without the addition time The concentration (EC 50 ) that caused the accumulation of 50 % cyclic AMP was calculated from the concentration-response curve by the least-squares method with the amount of AMP being 100% and 0%, respectively. Table 3 shows the results.
  • the compound of the present invention also has a stimulating effect on the human ⁇ 3 adrenergic receptor.
  • the compounds of the present invention are useful as) S 3 adrenergic receptor agonists as preventive and therapeutic agents for obesity, diabetes, irritable bowel syndrome, acute or chronic diarrhea, and the like.
  • the compounds of the present invention can also be used for improving symptoms such as abdominal pain, nausea, vomiting, and upper abdominal discomfort associated with peptic ulcer, acute or chronic gastritis, biliary dyskinesia, cholecystitis, etc. it can.
  • any of oral administration, parenteral administration and rectal administration can be used.
  • Oral administration is preferred, but the preferred dosage is the method of administration, the patient's symptom 'age, the form of treatment (prevention or treatment) Usually, it is 0.01 to 2 O mg / kg / day, preferably 0.1 to 1 O mg / kg /.
  • the compound of the present invention is usually administered in the form of a preparation prepared by mixing with a preparation carrier.
  • a preparation carrier a substance that is commonly used in the pharmaceutical field and does not react with the compound of the present invention is used. Specifically, for example, lactose, glucose, mannite, dextrin, starch, sucrose, magnesium aluminate metasilicate, synthetic aluminum gaterate, crystalline cellulose, sodium carboxymethyl cellulose, hydroxypropyl starch, carboxymethyl cellulose Calcium, ion exchange resin, methylcellulose, gelatin, gum arabic, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinylalcohol, light gay anhydride, magnesium stearate , Talc, carboxyvinyl polymer, titanium oxide, sorbitan fatty acid ester, sodium lauryl sulfate, glycerin, fatty acid glycerin ester,
  • Dosage forms include tablets, capsules, granules, powders, syrups, suspensions, suppositories, gels, injections and the like. These preparations are prepared according to a conventional method. In the case of liquid preparations, they may be in the form of being dissolved or suspended in water or other appropriate medium at the time of use. Tablets and granules may be coated by a known method. In the case of injections, it is prepared by dissolving a pharmaceutically acceptable acid addition salt of the compound represented by the above formula (I) in water, and dissolving it in an isotonic agent if necessary. PH adjusting agents, buffers and preservatives may be added. These preparations can contain the compound of the present invention in an amount of 0.01% or more, preferably 0.05 to 70%. These formulations may also contain other therapeutically active ingredients.
  • Example 4 The reaction and treatment were carried out in the same manner as in Example 1 using the corresponding indoles instead of 3- (2-aminoethyl) -16-fluoroindole in Example 1, and the product was recrystallized from a suitable solvent. Thus, the compounds shown in Table 4 were obtained.
  • the recrystallization solvent was ethanol for the compound of Example 4 and ethanol for all the remaining compounds. Table 4
  • Example 9 The following compound was obtained by reacting and treating in the same manner as in Example 8 using a starting compound having a specific configuration of 3- (2-aminobutyric pill) indole and 3-chloromandelic acid. .
  • the optical purity of the compound of the example was measured according to the method described in Example 9.
  • the following components are mixed, granulated, and compression-molded to prepare 1000 tablets of 10 Omg per tablet. '
  • Lactose 54 g
  • Microcrystalline cellulose 11 g :,
  • Pill cellulose in the mouth of hydroxy 3 g
  • Magnesium stearate 1 g.
  • Compounds obtained by the present invention, / S 3 has a highly selective 3 Adorenarin receptor stimulating effect on Adorenarin receptor, diabetes, obesity, irritable bowel syndrome, as a preventive and therapeutic agent, such as acute or chronic diarrhea It can also be used to improve symptoms such as abdominal pain, nausea, vomiting, and upper abdominal discomfort associated with peptic gallbladder, acute or penetrating gastritis, and the like.

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte à un dérivé de 2-[2-(indol-3-yl)éthylamino]-1-phényléthanol, représenté par la formule générale (I), ainsi qu'à un sel d'addition d'acide de ce composé qui soit acceptable sur le plan pharmaceutique. Dans cette formule (I), R1 représente halogène ou trifluorométhyle; R2 représente hydrogène, alkyle inférieur ou alkyle inférieur fluoré; et R3 représente hydrogène, halogène, trifluorométhyle, nitro ou cyano. Ce composé possède une activité hautement sélective de stimulation des récepteurs d'adrénaline β3 et il peut être utilisé pour traiter ou prévenir le diabète, l'obésité, le syndrome du côlon irritable, la diarrhée aiguë ou chronique, et autres, et également pour améliorer l'état de personnes souffrant de syndromes accompagnant un ulcère grastroduodénal, une gastrite aiguë ou chronique et autres troubles, tels que les douleurs abdominales, les nausées, les vomissements et les gênes épigastriques.
PCT/JP1994/001941 1994-11-17 1994-11-17 Derive de 2-[2-(indol-3-yl)ethylamino]-1-phenylethanol WO1996016038A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/JP1994/001941 WO1996016038A1 (fr) 1994-11-17 1994-11-17 Derive de 2-[2-(indol-3-yl)ethylamino]-1-phenylethanol
AU10341/95A AU1034195A (en) 1994-11-17 1994-11-17 2-{2-(indol-3-yl)ethylamino}-1-phenylethanol derivative

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PCT/JP1994/001941 WO1996016038A1 (fr) 1994-11-17 1994-11-17 Derive de 2-[2-(indol-3-yl)ethylamino]-1-phenylethanol

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000044721A1 (fr) * 1999-01-29 2000-08-03 Dainippon Pharmaceutical Co., Ltd. Derives indole 3, 7-de-substitues et compositions medicales les renfermant
WO2003106418A1 (fr) * 2002-06-01 2003-12-24 住友製薬株式会社 Indole, indazole, et derive benzazole

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J. ORG. CHEM., 56 (14), 4403-7, (1991). *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000044721A1 (fr) * 1999-01-29 2000-08-03 Dainippon Pharmaceutical Co., Ltd. Derives indole 3, 7-de-substitues et compositions medicales les renfermant
WO2003106418A1 (fr) * 2002-06-01 2003-12-24 住友製薬株式会社 Indole, indazole, et derive benzazole
JPWO2003106418A1 (ja) * 2002-06-12 2005-10-13 住友製薬株式会社 インドール、インダゾール、およびベンズアゾール類
US7217724B2 (en) 2002-06-12 2007-05-15 Dainippon Sumitomo Pharma Co., Ltd. Indole, indazole, and benzazole derivative

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