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【结 构 式】 
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【药物名称】AR-0598 【化学名称】trans-3-[4-(5-Amidino-1-benzofuran-2-ylcarboxamido)cyclohexyl]propionic acid ethyl ester 【CA登记号】 【 分 子 式 】C21H27N3O4 【 分 子 量 】385.46704 |
【开发单位】Mitsubishi Pharma (Originator) 【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Integrin alphaIIbbeta3 (Fibrinogen gpIIb/IIIa) Antagonists |
合成路线1
Pinner reaction of ethyl 5-cyano-2-benzofurancarboxylate (I) gave imidate (II) and subsequent treatment with ethanolic ammonia afforded amidine (III). After basic hydrolysis of the ester group of (III), protection with benzyl chloroformate provided the benzyloxycarbonyl derivative (IV). Coupling of (IV) with ethyl trans-3-(4-aminocyclohexyl)propionate (V) in the presence of EDC and HOBt yielded amide (VI). Finally, hydrogenolysis of the benzyloxycarbonyl protecting group of (VI) provided the title amidino ester.
| 【1】 Ono, S.; Yoshida, T.; Ashimori, A.; Kosaka, K.; Okada, T.; Maeda, K.; Eda, M.; Mori, F.; Inoue, Y.; Ebisu, H.; Imada, T.; Ikegawa, R.; Wang, F.; Nakamura, N. (Welfide Corporation); Novel fused-ring carboxylic acid cpds. or salt thereof,and medicinal use thereof. EP 0712844; JP 1996053398; JP 1996231548; US 5635527; US 5753670; WO 9533720 . |
| 【2】 Nakamura, N.; Imada, T.; Inoue, Y.; Kosaka, K.; Yoshida, T.; Ono, S.; Fukaya, C.; Maeda, K.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives. Chem Pharm Bull 1999, 47, 12, 1694. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
| (I) | 37353 | ethyl 5-cyano-1-benzofuran-2-carboxylate | C12H9NO3 | 详情 | 详情 | |
| (II) | 37354 | ethyl 5-[ethoxy(imino)methyl]-1-benzofuran-2-carboxylate | C14H15NO4 | 详情 | 详情 | |
| (III) | 37355 | ethyl 5-[amino(imino)methyl]-1-benzofuran-2-carboxylate | C12H12N2O3 | 详情 | 详情 | |
| (IV) | 37356 | 5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-carboxylic acid | C18H14N2O5 | 详情 | 详情 | |
| (V) | 37352 | tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate | C12H23NO3 | 详情 | 详情 | |
| (VI) | 37357 | ethyl 2-([4-[([5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-yl]carbonyl)amino]cyclohexyl]oxy)acetate | C28H31N3O7 | 详情 | 详情 |