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WO1985001289A1 - Derives de benzoxazolone et de benzothiazolone et leur procede de preparation - Google Patents

Derives de benzoxazolone et de benzothiazolone et leur procede de preparation Download PDF

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Publication number
WO1985001289A1
WO1985001289A1 PCT/JP1984/000452 JP8400452W WO8501289A1 WO 1985001289 A1 WO1985001289 A1 WO 1985001289A1 JP 8400452 W JP8400452 W JP 8400452W WO 8501289 A1 WO8501289 A1 WO 8501289A1
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WO
WIPO (PCT)
Prior art keywords
group
salt
benzoxazolone
lower alkyl
compound
Prior art date
Application number
PCT/JP1984/000452
Other languages
English (en)
Japanese (ja)
Inventor
Yoshihiko Kitaura
Teruo Oku
Yukihisa Baba
Chiyoshi Kasahara
Masashi Hashimoto
Original Assignee
Fujisawa Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Publication of WO1985001289A1 publication Critical patent/WO1985001289A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Definitions

  • the present invention relates to novel benzoxazolones and benzothiazone derivatives. More specifically, the present invention relates to novel benzoxazoconone and benzothiazozone derivatives having anti-inflammatory and antithrombotic effects, a process for producing them, and a process for producing them.
  • the invention relates to pharmaceutical compositions containing the same and to their use as medicaments in the treatment of inflammation or thrombosis in humans and animals.
  • one object of the present invention is to provide novel benzoxazolones and benzothiazolone derivatives which are useful as pharmaceuticals such as anti-inflammatory agents or antithrombotic agents. This is ⁇
  • Another object of the present invention is to provide a process for producing the benzoxoxa; ⁇ - and benzothiazolone derivatives.
  • Still another object of the present invention is to provide a pharmaceutical composition containing the benzoxazolone and the benzothiazolone derivative as active ingredients. .
  • Yet another object of the present invention is to provide a method of using benzoxazolone and benzothiazolone derivatives in the treatment of inflammation or thrombosis of humans and animals. What to provide
  • S 1 is a aryl group or a heterocyclic group which may have a suitable substituent
  • X is S or 0,
  • novel benzoxazolone and benzothiazone derivative (I) are produced by the production method represented by the following reaction formula! ? Can be manufactured.
  • R is a lower alkyl group
  • ⁇ represents a lower alkyl group,-represents S or, and represents an acid residue, respectively).
  • OMPI "Lower” shall mean a group having from 1 to 6 carbon atoms, unless otherwise indicated.
  • Suitable “lower alkyl group” is a linear or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethynole, propynole, Examples include isoppropinole, butynole, isobutynole, tertiary butyl, pentyl, hexyl, and the like, preferably those having 1 to 4 carbon atoms.
  • a preferred "lower alkoxy group” is a straight-chain or branched alkoxy group having 1 to 6 ⁇ -atoms, such as methoxy, ethoxy. , Butoxy, isopropoxy, butoxy, isobutoxy, tertiary butoxy, pentoxy, hexoxy, etc. It preferably has from 1 to 4 carbon atoms.
  • aryl groups include phenyl, trinole, xylyl, mesyl, and tarmenyl, and these "aryl groups” Is a halogen, such as fluorine, chlorine, bromine, or iodine; for example, methoxy, ethoxy, propoxy, isop sigma, and tertiary butane. It may have a suitable substituent such as a lower alkoxy group such as xyl. .
  • a preferred "heterocyclic group” has at least one heteroatom such as an oxygen atom, a zirconium atom, a nitrogen atom, etc., and is therefore referred to as “heterocyclic group”. Examples thereof include a “heteromonocyclic group” such as a 3- to 7-membered heteromonocyclic group containing phenyl or the like.
  • halogens such as fluorine, chlorine, bromine or iodine, for example, methoxy, ethoxy, propoxy, isopropoxy, tertiary Lower grades such as butoxy, etc.
  • alkoxy groups such as Trik sigma oxime, Trifnoremo oxime, 2, 2, 2 Tris (2,2,2) —tricyclo mouths—tri-mouth (lower) terrexoxy, amino, imidazolyl groups such as tertiary butoxy And the like.
  • the “acid residue” include, for example, a halogen such as fluorine, chlorine, bromine, or oxygen, and a sulfonyloxy group (for example, a methyl group).
  • a halogen such as fluorine, chlorine, bromine, or oxygen
  • a sulfonyloxy group for example, a methyl group.
  • Groups such as oxy group, ethanol group, benzene group, benzene group, benzene group, etc.).
  • Suitable "halogens” include chlorine, bromine, fluorine and oxygen.
  • Suitable salts of the target compound (I) are pharmaceutically acceptable salts, ie, common non-toxic salts, such as acetate, maleate, tartrate, methansulfonate Organic salts such as salts, benzenesulfonate, formate, and toluenesulfonate, for example, hydrochloride, hydrobromide, hydrobromide, Inorganic acid salts such as thiocyanates, sulfates, phosphates, etc., or amino acids such as, for example, alginine, azuno, 'raginic acid, glutamate, etc. And the like.
  • the process for producing the target compound (I) of the present invention will be described in detail below.
  • the target compound (la) or a salt thereof can be produced by reacting the compound ( ⁇ ) or a salt thereof with the compound (0 ⁇ ) or a salt thereof.
  • This reaction is usually carried out in the presence of luciferic acid, but the most preferred acid is polyphosphoric acid.
  • This reaction is preferably performed without a solvent.
  • polyphosphoric acid is used both as an acid and as a solvent.
  • the reaction temperature is not particularly limited, and the reaction is usually carried out at room temperature, under heating or under heating, or under heating.
  • the salt of the chemical compound ( ⁇ ) is, for example, an alkali metal salt such as sodium salt or potassium salt, for example, calcium salt or magnesium salt. Salts such as earth metal salts, etc.3 ⁇ 4Salts with inorganic bases, organic bases such as trimethinoleamine, triethynoleamine, pyridine And salts with an acid such as hydrochloric acid or hydrobromic acid.
  • Suitable salts of the target compound (la) and the outline thereof include those exemplified for the target compound (I). Manufacturing method 2
  • the target compound (I) or a salt thereof can be produced by reacting the compound (IV) or a salt thereof with the compound (V).
  • OMPI Preferable examples of the compound (V) include phosgene, carbonyl carbon fluoride, dimethyl carbonate, dimethyl chloroformate, methionyl chloroformate, chloroformic acid, and the like.
  • Echinole, ku ⁇ ⁇ Trichloromethinole formate, 1,2-chloroformate, urea, ⁇ , ⁇ , ⁇ -canole, etc. include:
  • This reaction is usually performed in the presence of a base.
  • Suitable bases include, for example, alkali metal hydrides such as sodium hydride, for example, alkali metal hydroxides such as sodium hydroxide and hydroxide hydroxide.
  • Alkali earth metal hydroxides such as magnesium hydroxide, calcium hydroxide, etc.
  • Alkali metals such as sodium carbonate, calcium carbonate, etc.
  • Alkali metal carbonates such as magnesium carbonate and calcium carbonate
  • Alkali metal carbonates such as sodium bicarbonate and potassium bicarbonate Bicarbonate, for example sodium acetate, aluminum acetate such as acetate acetate Metal acetate, for example magnesium phosphate, calcium phosphate, etc.
  • Calcium earth metal phosphates such as sodium hydrogen phosphate and hydrogen phosphate
  • Inorganic bases such as metal hydrogen phosphites, etc., and triaminoquinoamins such as, for example, trimethylammine, triethylamine, etc.
  • Organic bases such as picolin, piperidine, U-methylol.pi-lysine, N-methylolmonolefolin and the like.
  • This reaction is usually carried out in a solvent such as ethyl acetate, acetate, methyl ether, tetrahydrofuran, and toluene, If the solvent does not adversely affect the reaction,
  • the reaction can be performed in any other solvent.
  • the reaction temperature is not particularly limited, and the reaction is usually performed under rejection, normal temperature, heating or heating.
  • reaction is usually carried out in a solvent-free solvent while heating.
  • Suitable salts of the compounds include those exemplified for the target compound (I). Manufacturing method 3
  • the target compound (Ic) or a salt thereof can be produced by subjecting the compound (lb) or a salt thereof to an oxidation reaction.
  • oxidizing agent used in the reaction include hydrogen peroxide, perbenzoic acid, perphthalic acid, formic acid, peracetic acid, triflic acid persulfate, and meta-sigma. Peroxyacids such as perbenzoic acid are mentioned.
  • This reaction is usually carried out in a solvent such as acetic acid, chlorophoronem, dichloromethane, diethanolamine, dioxane or benzene.
  • a solvent such as acetic acid, chlorophoronem, dichloromethane, diethanolamine, dioxane or benzene.
  • the reaction can be performed in any other solvent that does not adversely affect the reaction.
  • the reaction temperature is not particularly limited, and the reaction is usually carried out under cooling, at room temperature, under heating or under heating.
  • Examples of the salt having a good interference with the target compounds () and (Ic) include those exemplified for the target compound (I). Manufacturing method 4
  • the compound (Ie) or a salt thereof can be produced by subjecting the compound (I) or a salt thereof to an ether cleavage reaction.
  • Suitable reagents to be used in this reaction include, for example, sigma hydrogen, such as hydrogen tribromide, and hydrogen halide, such as hydrogen bromide and hydrogen bromide. Examples includeucic acid.
  • This reaction is usually carried out in the form of edromethane, acetic acid, and anhydrides such as dichloro sigma methane, macroporous film, and, for example, diethyl ether ether and tetrahydrofuran. Performed in a solvent such as acetic acid.
  • a non-pitonic solvent such as dichromane, chloroform, polyester and the like.
  • the reaction temperature is not particularly limited, and the reaction is carried out under cooling, at room temperature, under heating or under heating.
  • Suitable salts of the compounds (Id) and (Ie) include those exemplified for the target compound (I). Manufacturing method 5
  • the target compound (Ig) or a salt thereof can be produced by subjecting the compound (If) or a salt thereof to an N-alkylation reaction.
  • the IT—Alkylating agent used in the alkylation reaction is, for example, mono (or di) -low, such as dimethyl sulfate.
  • OMPI Lower alkyl sulphonic acid (lower) alkyl esters such as methansulphonic acid methyl olester, etc. And ⁇ -genated (lower) alkyls such as methylated methyl and ethyl terephthalate.
  • This reaction is usually carried out in the presence of a base.
  • Suitable bases include alkaline metal hydrides, such as, for example, hydrogenated sodium hydride, for example, sodium methoxide, sodium methoxide, sodium hydroxide, etc.
  • Alkali metal alkoxides such as lithium tertiary butoxide, for example, Alkali metal hydroxides such as sodium hydroxide, hydroxide hydroxide, etc.
  • Alkaline earth metal hydroxides such as magnesium oxide and calcium hydroxide, for example, Alkali metal carbonates such as sodium carbonate and carbonated carbonate, for example Alkali metal carbonates such as magnesium carbonate, calcium carbonate, etc.Alkali metal bicarbonates such as sodium bicarbonate, bicarbonate lithium, etc.
  • Alkali metal acetates such as sodium acetate, potassium acetate, etc.
  • Alkaline earth metal phosphates such as calcium and calcium phosphate, for example, aluminum salts such as sodium phosphate sodium phosphate and sodium phosphate phosphate
  • Inorganic bases such as metal hydrogen phosphinates, and, for example, trimethylamine, triethylamine, triethylamine, picolini, and the like.
  • organic bases such as methacrylonitrile, pyrrolidine, methamine pyrrolidin, and methionolemorpholin.
  • This reaction is usually carried out in a solvent such as dichloromethane, chlorophoronelem, aceton, or jetinole ether,
  • the reaction can be performed in any other solvent that does not adversely affect the reaction.
  • the reaction temperature is not particularly limited, and the reaction is usually performed under cooling, at room temperature, or under heating.
  • Examples of suitable salts of the target compounds (If) and (Ig) include those exemplified for the target compound (I). Manufacturing method £
  • the target compound (If) or its salt is obtained by subjecting compound (1) or its salt to a ring-closing reaction! ) Can be manufactured.
  • the reagent used for this ring-closing reaction is, for example, an alkali metal azide such as sodium azide or a lithium azide, for example, diphenyloxyphosphorus Azide, di (p-trino-reoxy) resin, etc.
  • Azide derivatives such as di (lower) alkoxyphosphorinoleazide such as noreazide and jetkoxyphosphorinolazide.
  • This reaction is usually associated with toluene, xylene, N, N-dimethylaminophenol, for example, trimethylaminoamine, triethylamine, etc.
  • the reaction is carried out in a solvent such as triaminophenol or chlorophorone, but the reaction can be carried out in any other solvent that does not adversely affect the reaction. You can do it.
  • the reaction temperature is not particularly limited, and the reaction is usually performed under heating or heating.
  • suitable salts of compound W include salts with bases as exemplified for chemical compound (II).
  • Compound (E) can be produced by reacting compound ( ⁇ ) with compound ( ⁇ ).
  • This reaction is usually performed in the presence of a base.
  • Suitable bases are, for example, alkali metal hydrides such as sodium hydride, for example sodium methoxide, sodium methoxide, potassium hydride. Alcohols such as tertiary butoxy and other metal alkoxides, such as sodium hydroxide, hydroxylated lime and other metal hydroxides
  • alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide
  • alkaline metal carbonates such as sodium carbonate and potassium carbonate
  • Alkali earth metal carbonates such as magnesium carbonate and canecarbonate
  • Alkali metal carbonates such as sodium bicarbonate and hydrogencarbonate-lithium Alkali metal acetates, such as bicarbonates, for example sodium acetate, potassium acetate, etc.
  • Alkaline earth metal phosphates such as magnesium and calcium phosphate, for example, sodium phosphate sodium phosphate, dicalcium hydrogen phosphate, etc.
  • Inorganic bases such as alkali metal phosphoric acid hydrogen salts, and, for example, trimethylamine, trimethylamine, triethylamine, etc.
  • OMPI Organic bases such as peridine, N—methinole pyrrolidine, and N—methinole monolefolin.
  • the reaction is usually carried out with water, for example, methanol, ethanol, etc., acetic acid, acetate, dioxan, acetonitrinole, chlorophenol. , Dichloromethan, shiojiride ethylene, tetrahydrofuran, alcoholic acid, IT, N—dimethinole honolem amido pyridin
  • water for example, methanol, ethanol, etc., acetic acid, acetate, dioxan, acetonitrinole, chlorophenol. , Dichloromethan, shiojiride ethylene, tetrahydrofuran, alcoholic acid, IT, N—dimethinole honolem amido pyridin
  • the reaction is carried out in such conventional solvents, but the reaction can be carried out in any other organic solvent as long as it does not adversely affect the reaction.
  • the hydrophilic solvent may be used by mixing with water.
  • the base to be used is, for example, an alkali metal hydride such as hydrogen hydride, or a metal hydride such as sodium methoxide, sodium methoxide, or potassium hydride.
  • alkaline metal alcohols such as tertiary butoxy chloride
  • this reaction usually takes place, for example, in the presence of methanol, ethanol, etc.
  • the reaction temperature is not particularly limited, and the reaction is usually carried out under cooling, at room temperature, under heating or under heating. Production method of raw compound 2
  • Compound (X) can be produced by subjecting compound (K) to an ether cleavage reaction. This reaction can be carried out in substantially the same manner as in Production method 4.o Production method of starting compound 3
  • Compound (Fa) or a salt thereof can be produced by subjecting the compound to a reduction reaction.
  • This reduction reaction includes, for example, aluminum metal bisulfite such as sodium bisulfite or aluminum metal sulfide and ammonia such as sodium sulfide. Combination of near water, (2) combination of metal and organic acid,) catalytic reduction, etc.
  • this reaction is usually carried out with water, for example, methanol, ethanol, etc.
  • water for example, methanol, ethanol, etc.
  • the reaction is carried out in a solvent such as the above-mentioned solvent, but can be carried out in any other solvent that does not adversely affect the reaction.
  • suitable metals include iron, zinc, and the like
  • suitable organic acids include formic acid and acetic acid. And others.
  • Suitable catalysts include a catalyst such as a platinum metal catalyst such as platinum oxide and a palladium metal catalyst such as palladium-carbon.
  • Suitable salts of the compound (ffa) include those exemplified for the target compound (I).
  • the target compound of the present invention is a novel compound and has an anti-inflammatory effect and an antithrombotic effect.
  • the compounds of the invention are pharmaceutically acceptable, such as organic or inorganic solid or liquid excipients suitable for oral, parenteral administration or external use
  • the compound can be used in the form of a pharmaceutical preparation containing the compound as an active ingredient after being mixed with a carrier.
  • Pharmaceutical preparations include capsules, tablets, dragees, solutions, suspensions, emulsion and the like. If necessary, the above preparations may contain auxiliaries, stabilizers, wetting agents or emulsifiers, buffers and other commonly used additives.
  • the dose of the compound will vary depending on the age and condition of the patient, but the compounds of this invention will be irritated or irritated at an average single dose of about 10, 50, 100 mg 250, 500, 1000.
  • One-day zero force ratgenin (0. rat) was injected subcutaneously into the right hind paw to create force-lagenin foot edema.
  • the test drug was suspended in methylcellulose and given orally 60 minutes before the administration of ligamentin.
  • the foot volume was measured by a water displacement method by immersing the foot volume just above the peroneal malleolus using a blemistomometer (manufactured by Yugo Basil). The difference in paw volume between before and 3 hours after lactogenin administration was considered as edema volume. Test results are based on Student's t-test].
  • Oral administration was performed 60 minutes before.
  • the foot volume was measured by a water displacement method using a plethysmometer (made by Yugo Basil) and immersing it just above the peroneal malleolus.
  • the difference in paw volume between before administration of the antigen and antibody and 1 hour and 3 hours after administration was regarded as edema volume.
  • the test results were statistically analyzed and solved by Student's t-test.
  • Blood was collected from the central ear artery of male Japanese white rabbits weighing 2.5-3.0 ⁇ . 3.8 de for 9 volumes of blood. The blood was subjected to anticoagulation treatment by adding 1 volume of sodium citrate. Blood was centrifuged at 1300 rpm for 10 minutes at room temperature to prepare platelet-rich plasma. Platelet-poor plasma (PPP) obtained by further centrifuging blood at 3000 rpm for 10 minutes: PRP was diluted. The number of platelets in PRP used for the agglutination test was about 4 ⁇ 10 5 / raj !. Platelet aggregation was measured by a Bonn and Box turbidimetric method in a double channel aggregometer (Shenko, DP-247E).
  • a saline Z-blocker mixture (a block of PRP O.25 m plus saline 0.02) was stirred (100 rpm) during aggregation. The bottom was incubated at 37 C for 2 minutes and then the flocculant (0.03) was added. Platelet aggregation was measured by D-turbidimetry by recording the change in light transmittance during aggregation. The activity of the inhibitor was determined by the IC 5 () value, ie 50 de. It was expressed as the concentration required for the platelet aggregation inhibition response.
  • Arachidonic acid (Sigma II) was used as a flocculant at a final concentration of 5M.
  • Preferred embodiments of the target compound (I) are as follows.
  • Preferred embodiments of R 1 may have a halogen. ⁇ aryl group; or a heteromonocyclic group, more preferably fluorine or chlorine.
  • Preferred embodiments are a halogen, a lower alkyl group, a lower alkoxy group or a hydroxy group.
  • R 3 are hydrogen or lower alkyl groups o
  • K U PO Heat the mixture at ambient temperature and at 130 ° C for 1.5 hours with stirring. After cooling, pour the mixture into a mixture of ice and hydrochloric acid. The organic layer is separated, and the aqueous layer is extracted with cyclo- ⁇ -methane. Combine the organic layers, extract with 1 ⁇ sodium hydroxide, adjust the alkaline solution to PS 4 to 5 with concentrated hydrochloric acid, and then extract with dimethylmethane. The organic layer is washed with water, dried, and the solvent is distilled off under reduced pressure. The residue obtained is crystallized from benzene to give 3-benzoyl, 14-alkoxy-2-hydroxybenzoic acid. The acid (26.31 ⁇ ) is obtained as crystals.
  • Example 3 The following compound was obtained in the same manner as in Example 1.
  • Benzoinone 5 Chlorine 2 — Benzoxazolone (2.0 ⁇ ), methyl iodide (1.56 ⁇ ) and carbonic acid A suspension of lithium (1.51 ⁇ ) in anhydrous acetone (40) is stirred at room temperature for half an hour.
  • OMPI IE (Sujonore): 3260, 1 780, 1 76 OCOT -1 ⁇ (DMS 0- ⁇ 6, d): 2.30 (3H, s), 6.88 (1H, s),

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Nouveaux dérivés de benzoxazolone et de benzothiazolone représentés par la formule (I) (où R1 représente un aryle ou un groupe hétérocyclique possédant éventuellement un substituant approprié, R2 représente un halogène, un alkyle inférieur, un hydroxy ou un alkoxy inférieur, R3 représente de l'hydrogène ou un alkyle inférieur, X représente du soufre ou de l'oxygène et Y représente CO, S, SO2 ou NH), leurs sels, leur procédé de préparation, composition médicinale les contenant, et leur utilisation dans le traitement d'inflammations ou de thromboses chez l'homme et les animaux.
PCT/JP1984/000452 1983-09-22 1984-09-20 Derives de benzoxazolone et de benzothiazolone et leur procede de preparation WO1985001289A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8325370 1983-09-22
GB838325370A GB8325370D0 (en) 1983-09-22 1983-09-22 Benzoxazoline and benzothiazoline derivatives

Publications (1)

Publication Number Publication Date
WO1985001289A1 true WO1985001289A1 (fr) 1985-03-28

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AU (1) AU3431784A (fr)
GB (1) GB8325370D0 (fr)
IT (1) IT1176770B (fr)
WO (1) WO1985001289A1 (fr)

Cited By (20)

* Cited by examiner, † Cited by third party
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EP0249407A2 (fr) * 1986-06-09 1987-12-16 Pfizer Corporation Agents antiallergiques et anti-inflammatoires
JPH0283376A (ja) * 1988-09-19 1990-03-23 Pfizer Pharmaceut Co Ltd ベンゾオキサゾロン誘導体および抗アレルギー又は抗炎症組成物
EP0385664A2 (fr) * 1989-02-28 1990-09-05 Pfizer Inc. Benzoxazolones anti-inflammatoires
EP0395526A1 (fr) * 1989-04-28 1990-10-31 Adir Et Compagnie Nouveaux dérivés benzothiazolinoniques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
EP0409484A2 (fr) * 1989-07-20 1991-01-23 Pfizer Inc. Benzoxazolones 4,5,6,7-tétrasubstituées
EP0439265A1 (fr) * 1990-01-22 1991-07-31 Pfizer Inc. Composés 1,3-dicarbonyle et leur utilisation
US5141950A (en) * 1989-09-22 1992-08-25 Pfizer Inc. Benzimidazole compounds and their use
US5166353A (en) * 1989-04-28 1992-11-24 Adir Et Compagnie Benzothiazolinone compounds
US7022480B1 (en) 2001-10-11 2006-04-04 The Regents Of The University Of California Exons of the hSKCa3/KCNN3 gene
US8501953B2 (en) 2009-05-04 2013-08-06 Agios Pharmaceuticals, Inc PKM2 modulators for use in the treatment of cancer
US8742119B2 (en) 2009-04-06 2014-06-03 Agios Pharmaceuticals, Inc. Pyruvate kinase M2 modulators, therapeutic compositions and related methods of use
US8785450B2 (en) 2009-06-29 2014-07-22 Agios Pharmaceuticals, Inc. Therapeutic compounds and compositions
US8889667B2 (en) 2010-12-29 2014-11-18 Agios Pharmaceuticals, Inc Therapeutic compounds and compositions
US9115086B2 (en) 2009-06-29 2015-08-25 Agios Pharmaceuticals, Inc. Therapeutic compositions and related methods of use
US9181231B2 (en) 2011-05-03 2015-11-10 Agios Pharmaceuticals, Inc Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia
US9221792B2 (en) 2010-12-17 2015-12-29 Agios Pharmaceuticals, Inc N-(4-(azetidine-1-carbonyl) phenyl)-(hetero-) arylsulfonamide derivatives as pyruvate kinase M2 (PMK2) modulators
US9328077B2 (en) 2010-12-21 2016-05-03 Agios Pharmaceuticals, Inc Bicyclic PKM2 activators
US9365545B2 (en) 2013-03-15 2016-06-14 Agios Pharmaceuticals, Inc Therapeutic compounds and compositions
US9980961B2 (en) 2011-05-03 2018-05-29 Agios Pharmaceuticals, Inc. Pyruvate kinase activators for use in therapy
US11234976B2 (en) 2015-06-11 2022-02-01 Agios Pharmaceuticals, Inc. Methods of using pyruvate kinase activators

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FR2244507A1 (en) * 1973-06-26 1975-04-18 Inst Nat Sante Rech Med Chalcones and analogues - analgesics having low toxicity
JPS5069073A (fr) * 1973-06-26 1975-06-09
JPS5318539A (en) * 1976-08-03 1978-02-20 Hoechst Ag Process for manufacture of sulfuric halffester compound
JPS5697268A (en) * 1979-12-28 1981-08-05 Fujisawa Pharmaceut Co Ltd Lower alkanoic acid derivative, salt and preparation thereof and preventing agent and remedy for diabetic complication containing the same as active constituent
EP0049203A1 (fr) * 1980-09-29 1982-04-07 RIOM LABORATOIRES- C.E.R.M. (Société Anonyme) Nouvelles benzoxazolinones substituées en 6 par une chaîne aminoalcool ou aminocétone, leur préparation et leur application en thérapeutique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2244507A1 (en) * 1973-06-26 1975-04-18 Inst Nat Sante Rech Med Chalcones and analogues - analgesics having low toxicity
JPS5069073A (fr) * 1973-06-26 1975-06-09
JPS5318539A (en) * 1976-08-03 1978-02-20 Hoechst Ag Process for manufacture of sulfuric halffester compound
JPS5697268A (en) * 1979-12-28 1981-08-05 Fujisawa Pharmaceut Co Ltd Lower alkanoic acid derivative, salt and preparation thereof and preventing agent and remedy for diabetic complication containing the same as active constituent
EP0049203A1 (fr) * 1980-09-29 1982-04-07 RIOM LABORATOIRES- C.E.R.M. (Société Anonyme) Nouvelles benzoxazolinones substituées en 6 par une chaîne aminoalcool ou aminocétone, leur préparation et leur application en thérapeutique

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0249407A2 (fr) * 1986-06-09 1987-12-16 Pfizer Corporation Agents antiallergiques et anti-inflammatoires
EP0249407A3 (en) * 1986-06-09 1988-10-19 Pfizer Corporation Antiallergy and antiinflammatory agents
JPH0283376A (ja) * 1988-09-19 1990-03-23 Pfizer Pharmaceut Co Ltd ベンゾオキサゾロン誘導体および抗アレルギー又は抗炎症組成物
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GB8325370D0 (en) 1983-10-26
IT8422785A0 (it) 1984-09-21
AU3431784A (en) 1985-04-23
IT8422785A1 (it) 1986-03-21
IT1176770B (it) 1987-08-18

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