WO1995013264A1 - Derive d'acide hydroxamique et preparation medicamenteuse contenant ledit derive - Google Patents

Derive d'acide hydroxamique et preparation medicamenteuse contenant ledit derive Download PDF

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Publication number
WO1995013264A1
WO1995013264A1 PCT/JP1994/001870 JP9401870W WO9513264A1 WO 1995013264 A1 WO1995013264 A1 WO 1995013264A1 JP 9401870 W JP9401870 W JP 9401870W WO 9513264 A1 WO9513264 A1 WO 9513264A1
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group
carbon atoms
acid derivative
formula
hydroxamic acid
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PCT/JP1994/001870
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English (en)
Japanese (ja)
Inventor
Masashi Isozaki
Hiroaki Kasukawa
Keiichi Nakazawa
Keiko Houki
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Terumo Kabushiki Kaisha
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Publication of WO1995013264A1 publication Critical patent/WO1995013264A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Definitions

  • the present invention relates to a hydroxamic acid derivative having a smooth muscle cell growth inhibitory effect and effective as a blood vessel wall thickening inhibitor, and a pharmaceutical preparation containing the same.
  • Antithrombotic drugs and vasodilators are mainly used to improve the symptoms of angina pectoris and myocardial infarction, but narrowing of the blood vessel lumen and loss of elasticity caused by arteriosclerosis are used. It has not reached the point where it is fundamentally treated. There is currently no known drug capable of treating said condition. Therefore, there is a keen need for a drug capable of preventing or treating intimal hyperplasia causing blood vessel narrowing.
  • the present invention provides a compound which is useful as an anti-restenosis agent after PTCA operation, an anti-restenosis agent after autologous blood vessel or artificial blood vessel transplantation, and furthermore, a therapeutic or prophylactic agent for arteriosclerosis, and a vascular wall thickening containing the same as an active ingredient
  • the purpose is to provide prevention.
  • the present inventors have conducted intensive studies on the pharmacological activities of novel hydroxamic acid derivatives, and as a result, surprisingly, the hydroxamic acid compound of the present invention was found to be able to induce cultured smooth muscle cells induced by PDGF and serum. The present inventors have found that the growth inhibitory action is specifically suppressed, and completed the present invention.
  • the present invention is as follows.
  • a hydroxamic acid derivative represented by the following general formula (1) A hydroxamic acid derivative represented by the following general formula (1).
  • R 1 represents a phenyl group or an aryloxy unyl group, or the following general formula (2)
  • L represents an alkylene having 1 to 8 carbon atoms, and an alkyl group having 2 to 8 carbon atoms.
  • R 2 is hydrogen, carbon An alkyl group having 1 to 4 carbon atoms; an alkyl moiety having 1 to 4 carbon atoms, wherein M is hydrogen, Alcoyl group, alkoxycarbonyl group, and pharmaceutically acceptable cation.
  • R 3 represents an arylalkyl group having 1 to 4 carbon atoms in the aryl and alkyl portions.
  • alkylene refers to a divalent group derived from a linear or branched alkane, for example, one CH 2 —, one CHCH 3 —, —C (CH 3 ) 2 —, one CH (C 2 H 5) one one CH 2 CH 2 -, one CH 2 CHCH 3 - one C (CH 3) 2 C ( CH 3) 2-, one CH 2 CH 2 CH 2 -, and the like I do.
  • alkyl refers to a straight or branched chain group having 1 to 4 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group. , Isobutyl group, tert-butyl group and the like, but are not limited thereto.
  • alkoxy means one OR 4 (R 4 is an alkyl group), and is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a sec-butoxy group, an isobutoxy group, a tert group. Includes, but is not limited to, one butoxy group.
  • alkyne means one COR 4 (R 4 is an alkyl group) However, this includes, but is not limited to, formyl, acetyl, propionyl, butyryl, isobutyryl, bivaloyl and the like.
  • alkoxycarbonyl means one COR 5 (R 5 is an alkoxy group), which includes a methoxycarbonyl group, an ethoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, —Butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl and the like, but are not limited thereto.
  • aryl refers to a substituted or unsubstituted carbocyclic or heterocyclic aromatic group (substituents include halogeno group, nitro group, cyano group, alkyl group having 1 to 4 carbon atoms, carbon atom Selected from the group consisting of an alkoxy group of the numbers 1 to 4 and a halogen-substituted alkyl group), which includes a phenyl group, a mono- or 2-naphthyl group, a 2-, 3-mono- or 4-pyridyl group, a 0.2- or Include but are not limited to 3-furyl groups and the like.
  • aryloxy means one OR 6 (R 6 is an aryl group), including, but not limited to, phenoxy, 1-naphthoxy, 2-naphthoxy, and the like. Not something.
  • arylalkyl means an alkyl group bonded to an aryl group, and includes a phenylmethyl group (benzyl group), a 1-phenylethyl group, a 2-phenylethyl group, an 11-naphthylethyl group, Examples include, but are not limited to, 2-pyridylmethyl, benzhydryl and the like.
  • halogen means a group derived from a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • halogen-substituted alkyl refers to the above-mentioned alkyl group substituted with one or more halogen atoms, including a chloromethyl group, a trifluoromethyl group, a 2,2-difluoroethyl group and the like. But limited to these Not something.
  • “pharmaceutically acceptable cation” means a non-toxic cation, including, but not limited to, cations based on alkali and alkaline earth metals such as sodium, potassium, and magnesium. Not something.
  • a compound represented by the general formula (1) is obtained by adding a carboxylic acid activator to a carboxylic acid derivative represented by the following general formula (3).
  • the compound can be produced by reacting with a reactive derivative at the carboxyl group and then reacting with a hydroxyamine derivative represented by the following general formula (4).
  • R 2 in Formula 4 has the same meaning as in Formula (1), and Z represents a hydrogen atom or a suitable protecting group such as a benzyl group.
  • a compound in which L in the general formula (1) is represented by —CO— is obtained by reacting a carboxylic acid derivative represented by the following general formula (5) with a carboxylic acid activator to react with a carboxy group.
  • the derivative can be produced by introducing the derivative into a derivative and then reacting with a piperazine derivative represented by the following general formula (6).
  • R 2 and n in the formula 5 have the same meanings as in the general formula (1), and Z represents a hydrogen atom or a suitable protecting group such as a benzyl group.
  • examples of the carboxylic acid activator include thionyl chloride, phosphorus pentachloride, chloroformate ester (methyl methylformate, Ethyl formate), oxalyl chloride, carbodiimides (eg, N, N'-dicyclohexylcarbodiimide (DCC), 1-ethyl 3- (3-dimethylaminopropyl) carposimid (WSC))
  • carbodimids may be used in combination with N-hydroxybenzotriazole or imidoxysuccinic acid imide.
  • This reaction is usually carried out using halogenated hydrocarbons such as methylene chloride and chloroform, ethers such as tetrahydrofuran (THF), dioxane, dimethyl ether, getyl ether and isopropyl ether, and N, N-dimethylformamide.
  • halogenated hydrocarbons such as methylene chloride and chloroform
  • ethers such as tetrahydrofuran (THF), dioxane, dimethyl ether, getyl ether and isopropyl ether
  • N, N-dimethylformamide halogenated hydrocarbons
  • ethers such as tetrahydrofuran (THF), dioxane, dimethyl ether, getyl ether and isopropyl ether
  • N, N-dimethylformamide tetrahydrofuran
  • the reaction is performed in the presence of N, N-dimethylacetamide or a mixed solvent thereof.
  • the reaction temperature
  • reaction of the reactive derivative at the carboxyl group of the carboxylic acid derivative (3) with the hydroxyamine derivative (4), and the carboxyl group of the carboxylic acid derivative (5) The reaction between the reactive derivative and the piperazine derivative (6) in the above can be carried out, if the reaction derivative is an acid halide, in a solvent such as methylene chloride, tetrahydrofuran, acetone, or the like, using a deoxidizing agent (pyridine, triethylamine, carbon dioxide
  • the reaction is carried out under anhydrous or hydrous conditions in the presence of lium, hydrogen bicarbonate, sodium bicarbonate, etc.
  • the reaction temperature is from 150 ° C to 100 ° C, preferably from 10 ° C to 30 ° C.
  • the reaction may be performed in a solvent similar to the solvent used in the reaction of the carboxylic acid derivatives (3) and (5) with the carboxylic acid activating agent. it can.
  • the reaction temperature is usually 0 to 30 ° C
  • the reaction time is usually 1 to 5 hours.
  • the hydroxamic acid derivative (1) thus produced can be isolated and collected by means of separation and purification known per se (for example, chromatography and recrystallization).
  • the hydroxamic acid derivative of the present invention can be administered orally or parenterally (eg, intravenously, intramuscularly, subcutaneously) as an agent for preventing vascular wall thickening.
  • the dose of the active ingredient compound of the present invention varies depending on the age, weight, and condition of the patient, but is usually about 0.1 to 100 Omg / Kg, preferably 1 to 100 Omg / Kg per day. :! Administer up to 3 divided doses.
  • the compound of the present invention is used as an active ingredient or as one of the active ingredients, alone or together with a pharmaceutical carrier, by tablets, powders, capsules, granules, syrups, solutions, suspensions, injections, eye drops Or any formulation suitable for administration of suppositories and the like.
  • a pharmaceutical carrier include starch, sucrose, lactose, methylcellulose, carboxymethylcellulose, crystalline cellulose, sodium alginate, calcium hydrogen phosphate, magnesium metasilicate aluminate, anhydrous gay acid, and synthetic aluminum gayate.
  • Excipients hydroxypropyl cellulose, hydroxypropylmethylcellulose, gelatin and polyvinylpyrroli Binders such as dong; disintegrators such as calcium carboxymethylcellulose, crosslinked sodium carboxymethylcellulose and crosslinked polyvinylpyrrolidone; lubricants such as magnesium stearate and talc; cellulose acetate phthalate; hydroxypropyl methylcellulose acetate succinate , Coating agents such as methacrylic acid and methyl metaarinoleate copolymers, dissolution aids such as polyethylene glycol, sodium lauryl sulfate, lecithin, sorbitan monooleate, polyoxyethylene cetyl ether, sucrose fatty acid ester, and polyoxyethylene cured castor Emulsifiers such as oil and glyceryl monostearate; chelating agents such as EDTA; buffers; humectants; preservatives; cocoa butter and witebsol W 35 It can be mentioned a
  • N-benzyloxy N- (1-phenylethyl) 1-4- (3- (4-methoxyphenoxy) styryl) benzamide (1.5 g, 2.7 mmol) in methylene chloride (14 ml) was added to a solution of methylene chloride (14 ml) under ice-cooling.
  • a 1.0 M boron trichloride methylene chloride solution (3.24 ml, 3.24 mmol) was added dropwise, and the mixture was stirred at room temperature.
  • the reaction solution was evaporated under reduced pressure to obtain an ethyl acetate solution, washed with 1 N hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and an aqueous solution of saturated sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography.
  • the target compound (0.21 g) was obtained as a white solid (recrystallized from ethyl acetate-hexane) having the structure shown in the following formula (8) from the fraction eluted with methylene chloride and having the following properties: , 50.6%).
  • Mp 159-161 ° C
  • N-Isopropylhydroxyamine instead of N-methylhydroxyamine hydrochloride
  • the target compound having the structure shown in the following formula (9) and having the following properties was produced.
  • Example 2 According to the method of Example 2 except that N- (1-1 (2-furyl) ethyl) hydroxyamine hydrochloride is used instead of N-methylhydroxyamine hydrochloride, the structure is represented by the following formula (14). And the target compound having the following properties was produced.
  • N-acetoxy-N produced according to the method of Example 14 except that N-isopropylhydroxyamine hydrochloride was used instead of N-methylhydroxyamine hydrochloride.
  • Triisopropylamine (0.158 ml, 0.158 ml, 4-1 g) was added to a solution of cinnamamide (475 g, 0.942) in methylene chloride (10 ml) under stirring and ice cooling. 1.13 mmol) and acetyl chloride (0.737 ml, 1.04 mmol) were added, and the mixture was stirred for 1 hour.
  • the reaction mixture was added with ethyl acetate, washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • the structure was represented by the following formula (23) from the fraction eluted with methanol-chloroform, and the desired compound (0.81 g, 62.3%) was obtained as an oil having the following properties.
  • Example 14 except that 4-((4- (2- (4-methoxyphenyl) piperazinyl) methyl) cinnamic acid was used instead of 4-((4- (4-methylbenzhydryl) piperazinyl) methyl) cinnamic acid According to the above method, the target compound having the structure shown in the following formula (24) and the following properties was produced.
  • reaction solution was diluted with methylene chloride, washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. From the fraction eluted with methylene chloride, N-benzyloxy N— (1-phenylethyl) 1-4
  • Triethyl phosphite (20.6 ml, 0.12 inol) was added to the above ester, and the mixture was stirred at 130 ° C. for 3.5 hours.
  • the reaction mixture was added with ethyl acetate, washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • the residue obtained was subjected to silica gel chromatography and eluted with methylene chloride. From the fraction, 41 (diethoxyphosphorylmethyl) benzoic acid methyl ester (22.7 g, 79. 3%).
  • the medial smooth muscle layer was removed from the thoracic aorta of a 6-week-old Wistar male rat (manufactured by Charles River Japan Co., Ltd.), cut into 1 dragon 2 sections, and then cultured in 25 cm 3 2-12 weeks at 37 ° C 95% 0 2 + in Dulbec co-modified eagle medium (DMEM: Nissui) containing 10% serum. at 5% C0 2 under conditions extending from c slices cultured in Inkyubeta one, was collected divided cells as a primary cultured smooth muscle cells.
  • DMEM Dulbec co-modified eagle medium
  • the cultured smooth muscle cells were seeded on a 24-well plate (Falcon) at a ratio of 8 ⁇ 10 3 smooth muscle cell holes / 700 // 1 DMEM. After overnight, the cells were serum-free and cultured in an incubator for 2 days. Under these conditions Byon, the cell cycle of cultured smooth muscle cells goes into the Go phase (resting phase) and does not divide.
  • the hydroxamic acid derivative was dissolved in DMSO, diluted 100-fold with 10% serum + DMEM, and further diluted 20-fold with 10% serum + DMEM. That is, a 2000-fold dilution test solution was added to the cells under the above conditions, and after culturing for 4 days, the number of cells was counted with a Coulter counter (manufactured by Kakkiki Co., Ltd.). The result
  • the compounds of the present invention markedly suppressed the proliferation action of cultured smooth muscle cells.
  • the 50% inhibitory concentration is defined as 100% of the cultured smooth muscle cell proliferation ability when the compound of the present invention is not introduced, by introducing the hydroxamic acid derivative.
  • Acute toxicity tests were performed by oral and intravenous administration in ICR male mice (5-week-old).
  • the LD 5 () value of the compound of the present invention was 100 Omg / kg or more in both cases. Higher safety was confirmed compared to.
  • novel hydroxamic acid derivative according to the present invention and a vascular wall thickening inhibitor containing the same can be effectively used as an agent for preventing restenosis after PTCA operation and thus as a therapeutic agent for arteriosclerosis.

Abstract

Dérivé d'acide hydroxamique de formule générale (1) et préparation médicamenteuse contenant ledit dérivé ayant pour effet de supprimer la croissance des muscles lisses et utilisable pour prévenir l'épaississement des parois vasculaires et la resténose post-angioplastie coronarienne transluminale percutanée, et comme agent de lutte contre l'artériosclérose. Dans la formule (1), R1 représente phényle, aryloxyphényle ou un groupe de formule générale (2) dans laquelle R3 représente aryle ou arylalkyle dont le groupe alkyle possède de 1 à 4 atomes de carbone; K représente alkylène C¿1?-C8, alcénylène C2-C8, -(CH2)m-O- dans laquelle m est un nombre entier de 0 à 4 ou -CO-; n représente un nombre entier valant 0 ou 1; R?2¿ représente hydrogène, alkyle C¿1?-C4, ou arylalkyle dont le groupe alkyle possède de 1 à 4 atomes de carbone et M représente hydrogène, alcoyle, alcoxycarbonyle ou un cation pharmaceutiquement acceptable.
PCT/JP1994/001870 1993-11-08 1994-11-04 Derive d'acide hydroxamique et preparation medicamenteuse contenant ledit derive WO1995013264A1 (fr)

Applications Claiming Priority (4)

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JP5/278168 1993-11-08
JP27816893 1993-11-08
JP2247594 1994-02-21
JP6/22475 1994-02-21

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Cited By (10)

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WO1999005109A1 (fr) * 1997-07-25 1999-02-04 Tsumura & Co. Derives de pyridylacrylamide, remedes contre la nephrite et inhibiteurs de tgf-beta contenant lesdits elements
US6451801B1 (en) 1999-03-26 2002-09-17 Ucb, S.A. Compounds and methods for treatment of asthma, allergy and inflammatory disorders
US6541661B1 (en) 1999-11-23 2003-04-01 Methylgene, Inc. Inhibitors of histone deacetylase
US6686502B1 (en) 1999-03-26 2004-02-03 Ucb S.A. Compounds and methods for treatment of asthma, allergy and inflammatory disorders
WO2004063169A1 (fr) * 2003-01-13 2004-07-29 Astellas Pharma Inc. Derives d'acide hydroxamique utilises comme inhibiteurs de l'histone desacetylase (hdac)
WO2006037761A1 (fr) * 2004-10-01 2006-04-13 Dac S.R.L. Nouveaux inhibiteurs des histone-deacetylases
JP2009531393A (ja) * 2006-03-31 2009-09-03 ダック ソシエタ ア レスポンサビリタ リミタータ 癌の処置用のヒストンデアセチラーゼ阻害剤としての、ｎ−ヒドロキシ−３−（４−｛３−フェニル−ｓ−オキソ−プロペニル｝−フェニル）−アクリルアミド誘導体及びその関連化合物
US7750155B2 (en) 2006-02-07 2010-07-06 Astellas Pharma Inc. Pyrazinyl hydroxyacrylamide compounds having an inhibitory effect on the activity of histone deacetylase
US8242175B2 (en) 2004-10-01 2012-08-14 Dac S.R.L. Class of histone deacetylase inhibitors
US9745253B2 (en) 2015-03-13 2017-08-29 Forma Therapeutics, Inc. Alpha-cinnamide compounds and compositions as HDAC8 inhibitors

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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999005109A1 (fr) * 1997-07-25 1999-02-04 Tsumura & Co. Derives de pyridylacrylamide, remedes contre la nephrite et inhibiteurs de tgf-beta contenant lesdits elements
US6451801B1 (en) 1999-03-26 2002-09-17 Ucb, S.A. Compounds and methods for treatment of asthma, allergy and inflammatory disorders
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