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【结 构 式】 
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【药物名称】 【化学名称】N-[3(R)-Amino-2(S)-hydroxy-5-methylhexanoyl]-L-prolyl-L-alaninamide 【CA登记号】 【 分 子 式 】C15H28N4O4 【 分 子 量 】328.41481 |
【开发单位】Pfizer (Originator) 【药理作用】Cardioprotective Agents, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Aminopeptidase P Inhibitors |
合成路线1
The compound was prepared by solid phase peptide synthesis on a p-methylbenzhydrylamine resin. Attachment of Boc-L-alanine (I) afforded resin (II). Subsequent deprotection of the Boc group of (II) gave the alanine-linked resin (III). Coupling of (III) with Boc-L-proline (IV), followed by Boc group cleavage yielded the dipeptide resin (V). Further coupling of (V) with N-Boc-(2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid (VI) furnished the tripeptide resin (VI). Finally, deprotection of the Boc group of (VI) and simultaneous cleavage from the resin by treatment with HF provided the title tripeptide amide.
| 【1】 Maggiora, L.L.; Simmons, W.H.; Orawski, A.T.; Apstatin analogue inhibitors of aminopeptidase P, a bradykinin-degrading enzyme. J Med Chem 1999, 42, 13, 2394. |
| 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) | 26450 | Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid | 15761-38-3 | C8H15NO4 | 详情 | 详情 |
| (II) | 35168 | tert-butyl (1S)-2-amino-1-methyl-2-oxoethylcarbamate | C8H16N2O3 | 详情 | 详情 | |
| (III) | 35169 | (2S)-2-aminopropanamide | C3H8N2O | 详情 | 详情 | |
| (IV) | 16734 | (2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid | C10H17NO4 | 详情 | 详情 | |
| (V) | 35170 | (2S)-N-[(1S)-2-amino-1-methyl-2-oxoethyl]-2-pyrrolidinecarboxamide | C8H15N3O2 | 详情 | 详情 | |
| (VI) | 35171 | (2S,3R)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-5-methylhexanoic acid | C12H23NO5 | 详情 | 详情 | |
| (VII) | 35172 | tert-butyl (1R)-1-[(1S)-2-[(2S)-2-([[(1S)-2-amino-1-methyl-2-oxoethyl]amino]carbonyl)pyrrolidinyl]-1-hydroxy-2-oxoethyl]-3-methylbutylcarbamate | C20H36N4O6 | 详情 | 详情 |