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【结 构 式】

【药物名称】MEN-11467

【化学名称】N-[2-(4-Methylphenyl)acetyl]-N-methyl-(3-naphthyl)-L-alanine N-[2-(1H-indol-3-ylcarboxamido)cyclohexyl]amide

【CA登记号】

【 分 子 式 】C38H40N4O3

【 分 子 量 】600.7675

【开发单位】Menarini (Originator)

【药理作用】Asthma Therapy, Chronic Obstructive Pulmonary Diseases (COPD), Treatment of, RESPIRATORY DRUGS, Tachykinin NK1 Antagonists

合成路线1

3-Indolylcarboxylic acid (I) was converted to acid chloride (II) with oxalyl chloride in refluxing CH2Cl2, and subsequently condensed with cis 1,2-cyclohexanediamine (III) to provide racemic amide (IV). Coupling of (4-methylphenyl)acetyl chloride (VI) with D-3-(2-naphthyl)alanine (V) was carried out via previous silylation of the amino acid with bis(trimethylsilyl)acetamide in THF. The resulting amide (VII) was N-alkylated with ICH3 in the presence of NaH to provide (VIII). Then, the chiral acyl amino acid (VIII) was coupled to racemic amine (IV) using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide-HCl (EDC) and 7-aza-1-hydroxybenzotriazole (HOAt) to furnish the corresponding amide as a diastereomeric mixture, from which the desired isomer was isolated by reverse phase chromatography.

1 Potier, E.; Fincham, C.; Sisto, A.; Terracciano, R. (Menarini Industrie Farma Riunite srl); Pseudo-peptide cpds. as antagonists of neurokinines. WO 9845262 .
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) 17152 1H-Indole-3-carboxylic acid; Indole-3-Carboxylic acid; 3-Indolecarboxylic acid 771-50-6 C9H7NO2 详情 详情
(II) 17153 1H-indole-3-carbonyl chloride C9H6ClNO 详情 详情
(III) 21014 cis-1,2-Diaminocyclohexane; (1R,2S)-1,2-cyclohexanediamine; (1R,2S)-2-aminocyclohexylamine 1436-59-5 C6H14N2 详情 详情
(IV) 21015 N-[(1S,2R)-2-aminocyclohexyl]-1H-indole-3-carboxamide C15H19N3O 详情 详情
(V) 21016 (2R)-2-amino-3-(2-naphthyl)propionic acid; D-3-(2-Naphthyl)alanine 76985-09-6 C13H13NO2 详情 详情
(VI) 21017 2-(4-methylphenyl)acetyl chloride 35675-44-6 C9H9ClO 详情 详情
(VII) 21018 (2R)-2-[[2-(4-methylphenyl)acetyl]amino]-3-(2-naphthyl)propionic acid C22H21NO3 详情 详情
(VIII) 21019 (2R)-2-[methyl[2-(4-methylphenyl)acetyl]amino]-3-(2-naphthyl)propionic acid C23H23NO3 详情 详情
Extended Information