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【结 构 式】 
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【药物名称】Montirelin, CNK-602A, PS-24, CG-3703 【化学名称】N-[[(3R,6R)-6-Methyl-5-oxo-3-thiomorpholinyl]carbonyl]-L-histidyl-L-prolinamide 【CA登记号】90243-66-6, 62305-91-3 (undefined stereoch.) 【 分 子 式 】C17H24N6O4S 【 分 子 量 】408.48263 |
【开发单位】Grünenthal (Originator), Nippon Shinyaku (Licensee) 【药理作用】CNS Stimulants, PSYCHOPHARMACOLOGIC DRUGS, Sleep Disorders, Treatment of, TRH Analogs |
合成路线1
The synthesis of thyrotropin releasing hormone (TRH) analogues is described as follows: The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/C in methanol gives prolinamide (II), which is condensed with N-benzyloxy-carbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV). The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with 6-methyl-5-oxothiomorpholinyl-3-carboxylic acid (VI) by means of 1-hydroxybenzotriazole, dicyclohexylcarbodiimide and triethylamine in DMF.
| 【1】 US 4045556 . |
| 【2】 Goren, H.J.; Bauce, L.G.; Synthesis of a series of residue 1-(pyroglutamic acid) analogs of thyrotropin releasing hormone. Intl J Pept Protein Res 1979, 14, 216-226. |
| 【3】 Pento, J.T.; CG-3703. Drugs Fut 1983, 8, 12, 1007. |
| 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) | 36136 | benzyl (2S)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate | 34079-31-7 | C13H16N2O3 | 详情 | 详情 |
| (II) | 36137 | (2S)-2-pyrrolidinecarboxamide;L-prolinamide | 7531-52-4 | C5H10N2O | 详情 | 详情 |
| (III) | 36138 | benzyl (1S)-2-hydrazino-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | 49706-31-2 | C14H17N5O3 | 详情 | 详情 |
| (IV) | 36139 | benzyl (1S)-2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | C19H23N5O4 | 详情 | 详情 | |
| (V) | 31253 | (2S)-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-pyrrolidinecarboxamide | C11H17N5O2 | 详情 | 详情 | |
| (VI) | 36140 | (3R,6R)-6-methyl-5-oxo-3-thiomorpholinecarboxylic acid | C6H9NO3S | 详情 | 详情 |