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【结 构 式】

【药物名称】Wy-44221

【化学名称】(S,S)-1-(2-Methyl-3-sulfanyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acid
      (S,S)-1-(2-Methyl-3-sulfanyl-1-oxopropyl)indoline-2-carboxylic acid
      (S,S)-1-(2-Methyl-3-sulfanylpropionyl)indoline-2-carboxylic acid
      (S,S)-1-(3-Mercaptoisobutyryl)indoline-2-carboxylic acid

【CA登记号】78779-29-0 ((-)-enantiomer)

【 分 子 式 】C14H17NO3

【 分 子 量 】247.29649

【开发单位】Wyeth Pharmaceuticals (Originator)

【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Angiotensin-I Converting Enzyme (ACE) Inhibitors

合成路线1

The esterification of indoline-2-carboxylic acid (I) with ethanol HCl gives the corresponding ethyl ester (II), which is acylated with 3-(benzoylthio)-2-methylpropionyl chloride (III) by means of K2CO3 in methylene chloride yielding ethyl N-[3-(benzoylthio)-2-methylpropionyl]indoline-2-carboxylate (IV). The deprotection of (IV) with hydrazine in the same solvent affords ethyl N-(3-mercapto-2-methylpropionyl)indoline-2-carboxylate (V), which is finally saponified with KOH in methanol water.

1 Stanton, J.L.; et al.; Angiotensin converting enzyme inhibitors: N-Substituted monocyclic and bibyvlic amino acid deivatives. J Med Chem 1983, 26, 9, 1267-77.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 34307 (2S)-2,3-dihydro-1H-indole-2-carboxylic acid C9H9NO2 详情 详情
(II) 34308 ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate C11H13NO2 详情 详情
(III) 34309 S-[(2S)-3-chloro-2-methyl-3-oxopropyl] benzenecarbothioate C11H11ClO2S 详情 详情
(IV) 34310 ethyl (2S)-1-[(2R)-3-(benzoylsulfanyl)-2-methylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylate C22H23NO4S 详情 详情
(V) 34311 ethyl (2S)-1-[(2R)-2-methyl-3-sulfanylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylate C15H19NO3S 详情 详情

合成路线2

This compound can be obtained by several related ways: 1) The hydrolysis of ethyl indoline 2 carboxylate (I) with KOH in aqueous DMSO gives indoline 2-carboxylic acid (II), which is acylated with 3-(benzoylthio)-2-methylpropanoyl chloride (III) in methylene chloride yielding 1-[3-(benzoylthio)-2-methyl-1-oxopropyl]indoline-2-carboxylic acid (IV). Finally, this compound is debenzoylated by treatment with 2-methoxyethylamine (A). 2) The acylation of (I) with methacryloyl chloride (V) by means of triethylamine in ether yields ethyl 1-methacryloylindoline-2-carboxylate (VI), which is hydrolyzed with KOH in aqueous DMSO affording 1-methacryloylindoline-2-carboxylic acid (VII). Finally, this compound is treated with thiobenzoic acid (VIII) and 4-dimethylaminopyridine in acetone to give (IV), previously synthesized. 3) The acylation of acid (II) with (V) as before also gives (VII).

1 Kim, D.H.; et al.; Mercaptopropanoyl)indoline-2-carboxylic acids and related compounds as potent angiotensin converting enzyme inhibitors and antihypertensive agents. J Med Chem 1983, 26, 3, 394-403.
2 Serradell, M.N.; Castaner, J.; Blancafort, P.; WY-44221. Drugs Fut 1983, 8, 11, 953.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 34675 2-methoxyethylamine; 2-methoxy-1-ethanamine 109-85-3 C3H9NO 详情 详情
(I) 34308 ethyl (2S)-2,3-dihydro-1H-indole-2-carboxylate C11H13NO2 详情 详情
(II) 34307 (2S)-2,3-dihydro-1H-indole-2-carboxylic acid C9H9NO2 详情 详情
(III) 34309 S-[(2S)-3-chloro-2-methyl-3-oxopropyl] benzenecarbothioate C11H11ClO2S 详情 详情
(IV) 36214 (2S)-1-[(2R)-3-(benzoylsulfanyl)-2-methylpropanoyl]-2,3-dihydro-1H-indole-2-carboxylic acid C20H19NO4S 详情 详情
(V) 33553 2-methylacryloyl chloride 920-46-7 C4H5ClO 详情 详情
(VI) 36211 ethyl (2S)-1-methacryloyl-2,3-dihydro-1H-indole-2-carboxylate C15H17NO3 详情 详情
(VII) 36212 (2S)-1-methacryloyl-2,3-dihydro-1H-indole-2-carboxylic acid C13H13NO3 详情 详情
(VIII) 36213 benzenecarbothioic S-acid 98-91-9 C7H6OS 详情 详情
Extended Information