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【结 构 式】 
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【药物名称】PAT-5A 【化学名称】(E)-5-[4-[1-(2-Pyridyl)pyrrolidin-2(S)-ylmethoxy]benzylidene]thiazolidine-2,4-dione maleate 【CA登记号】199117-51-6, 199117-46-9 (free base), 199117-53-8 (monoHCl), 199117-54-9 (monoNa salt) 【 分 子 式 】C24H23N3O7S 【 分 子 量 】497.53081 |
【开发单位】Dr. Reddy's Research Foundation (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, PPARgamma Agonists, Thiazolidinediones (Glitazones) |
合成路线1
2-Chloropyridine (I) was condensed with (S)-prolinol (II) to furnish the pyridinylpyrrolidine (III). Subsequent alkylation of the hydroxyl group of (III) with 4-fluorobenzaldehyde (IV) using NaH in hot DMF gave ether (V). Knoevenagel condensation of (V) with 2,4-thiazolidinedione (VI) in the presence of benzoic acid and piperidine afforded the required benzylidene thiazolidine, which was finally treated with maleic acid in acetone to yield the title maleate salt.
| 【1】 Reddy, A.S.; Lohray, B.B.; Bhushan, V.; et al.; Novel euglycemic and hypolipidemic agents. 4. Pyridyl- and quinolinyl-containing thiazolidinediones. J Med Chem 1999, 42, 14, 2569. |
| 【2】 Ramanujam, R.; Lohray, B.B.; Alla, S.R.; Chakrabarti, R.; Paraselli, R.B.; Lohray, V.B. (Dr. Reddy's Research Foundation); Thiazolidinedione cpds. having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. thereof. WO 9741120 . |
| 【3】 Rao, P.B.; Ramanujam, R.; Alla, S.R.; Lohray, V.B.; Chakrabarti, R.; Lohray, B.B. (Dr. Reddy's Research Foundation); Heterocyclic cpds. having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. containing them. US 5919782 . |
| 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) | 17503 | 2-chloropyridine | 109-09-1 | C5H4ClN | 详情 | 详情 |
| (II) | 21347 | (2S)pyrrolidinylmethanol | 23356-96-9 | C5H11NO | 详情 | 详情 |
| (III) | 34806 | [(2S)-1-(2-pyridinyl)pyrrolidinyl]methanol | C10H14N2O | 详情 | 详情 | |
| (IV) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (V) | 34807 | 4-[[(2S)-1-(2-pyridinyl)pyrrolidinyl]methoxy]benzaldehyde | C17H18N2O2 | 详情 | 详情 | |
| (VI) | 10883 | 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione | 2295-31-0 | C3H3NO2S | 详情 | 详情 |