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【结 构 式】 
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【药物名称】GW-432042 【化学名称】S-[2-(1-Iminoethylamino)-1(R)-methylethyl]-L-cysteine 【CA登记号】251325-08-3, 251325-24-3 (diHCl) 【 分 子 式 】C8H17N3O2S 【 分 子 量 】219.30759 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Inducible Nitric Oxide Synthase (NOS-2) Inhibitors |
合成路线1
Alkylation of N-Boc-L-cysteine tert-butyl ester (I) with the chiral tosylate (II) gave thioether (III). The N-benzyloxycarbonyl protecting group of (III) was then cleaved by transfer hydrogenolysis using ammonium formate in the presence of Pearlman's catalyst to afford amine (IV). Condensation of this amine with the thioacetimidate (V) gave rise to amidine (VI). The N-Boc and tert-butyl ester protecting groups of (VI) were finally removed by treatment with a solution of HCl in dioxan.
| 【1】 Young, R.J.; et al.; Inhibition of inducible nitric oxide synthase by acetamidine derivatives of branched hetero-substituted lysine analogs. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 250. |
| 【2】 Beswick, P.J.; Young, R.J.; Kleanthous, S. (Glaxo Group Ltd.); Nitric oxide synthase inhibitors. EP 1084104; WO 9962875 . |
| 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) | 42195 | tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropanoate | C12H23NO4S | 详情 | 详情 | |
| (II) | 49913 | (1S)-2-[[(benzyloxy)carbonyl]amino]-1-methylethyl 4-methylbenzenesulfonate | C18H21NO5S | 详情 | 详情 | |
| (III) | 49914 | tert-butyl (2R)-3-[((1R)-2-[[(benzyloxy)carbonyl]amino]-1-methylethyl)sulfanyl]-2-[(tert-butoxycarbonyl)amino]propanoate | C23H36N2O6S | 详情 | 详情 | |
| (IV) | 49915 | tert-butyl (2R)-3-[[(1R)-2-amino-1-methylethyl]sulfanyl]-2-[(tert-butoxycarbonyl)amino]propanoate | C15H30N2O4S | 详情 | 详情 | |
| (V) | 42175 | 1-naphthylmethyl ethanimidothioate | C13H13NS | 详情 | 详情 | |
| (VI) | 49916 | tert-butyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[(1R)-2-(ethanimidoylamino)-1-methylethyl]sulfanyl]propanoate | C17H33N3O4S | 详情 | 详情 |