|
【结 构 式】 
|
【药物名称】 【化学名称】5-[4-(5-Methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]thiazolidine-2,4-dione hydrochloride 【CA登记号】172647-71-1 (free base), 172647-73-3 (fumarate), 193544-60-4 (fumarate salt (1:1)), 172647-72-2 (HCl), 193544-59-1 (monoHCl) 【 分 子 式 】C19H19ClN4O4S 【 分 子 量 】434.90468 |
【开发单位】Sankyo (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Glucose Lowering Agents, Thiazolidinediones (Glitazones) |
合成路线1
Selective substitution of the 2-chloro group of 2,6-dichloro-3-nitropyridine (I) by methylamine gave 6-chloro-2-(methylamino)-3-nitropyridine (II). The 6-chloro group of (II) was then displaced by sodium methoxide to afford methyl ether (III). The nitro group of (III) was reduced by catalytic hydrogenation, and the resulting diamine (IV) was cyclized with glycolic acid to furnish the imidazopyridine (V). Mitsunobu coupling of alcohol (V) with 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione (VI) produced the corresponding ether (VII). The title compound was then obtained by acid deprotection of the trityl group of (VII), followed by conversion to the hydrochloride salt.
| 【2】 Wada, K.; Oguchi, M.; Honma, H.; et al.; Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones. J Med Chem 2000, 43, 16, 3052. |
| 【1】 Fujita, T.; Fujimoto, K.; Yoshioka, T.; Yanagisawa, H.; Fujiwara, T.; Horikoshi, H.; Oguchi, M.; Wada, K. (Sankyo Co., Ltd.); Heterocyclic cpds. having antidiabetic activity, their preparation and their use. CA 2146701; EP 0676398; JP 1995330728; US 5624935; US 5834501; US 5962470; US 6117893 . |
| 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) | 13574 | 2,6-Dichloro-3-nitropyridine | 16013-85-7 | C5H2Cl2N2O2 | 详情 | 详情 |
| (II) | 44762 | N-(6-chloro-3-nitro-2-pyridinyl)-N-methylamine; 6-chloro-N-methyl-3-nitro-2-pyridinamine | C6H6ClN3O2 | 详情 | 详情 | |
| (III) | 44763 | 6-methoxy-N-methyl-3-nitro-2-pyridinamine; N-(6-methoxy-3-nitro-2-pyridinyl)-N-methylamine | C7H9N3O3 | 详情 | 详情 | |
| (IV) | 44764 | N-(3-amino-6-methoxy-2-pyridinyl)-N-methylamine; 6-methoxy-N(2)-methyl-2,3-pyridinediamine | C7H11N3O | 详情 | 详情 | |
| (V) | 44765 | (5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methanol | C9H11N3O2 | 详情 | 详情 | |
| (VI) | 18803 | 5-(4-hydroxybenzyl)-3-trityl-1,3-thiazolidine-2,4-dione | C29H23NO3S | 详情 | 详情 | |
| (VII) | 44767 | 5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | C38H32N4O4S | 详情 | 详情 |