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【结 构 式】 
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【药物名称】PNU-107859 【化学名称】N-Methyl-3-phenyl-2(S)-[3-(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)ureido]propionamide 【CA登记号】198700-58-2 【 分 子 式 】C13H15N5O2S2 【 分 子 量 】337.4248 |
【开发单位】Pfizer (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Matrix Metalloproteinase Inhibitors |
合成路线1
The reaction of L-phenylalanine methyl ester (I) with phosgene and pyridine in dichloromethane gives the isocyanate (II) (1), which is condensed with 5-amino-1,3,4-thiadiazol-2(3H)-thione (III) in THF to yield the urea (IV). Finally, this compound is treated with methylamine in ethanol to affords the target compound.
| 【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525. |
| 【2】 Jacobsen, E.J.; Mitchell, M.A.; Schostarez, H.J.; Harper, D.E. (Pharmacia & Upjohn AB); Thiadiazolyl(thio)ureas useful as matrix metalloprotease inhibitors. EP 0900211; JP 2000509039; WO 9740031 . |
| 【3】 Mitchell, M.A.; Schostarez, H.J.; Harper, D.E.; Jacobsen, E.J. (Pharmacia Corp.); Thiadiazole derivs. useful for the treatment of diseases related to connective tissue degradation. US 5847148 . |
| 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) | 12324 | methyl (2R)-2-amino-3-phenylpropanoate | 21685-51-8 | C10H13NO2 | 详情 | 详情 |
| (II) | 38888 | methyl (2S)-2-isocyanato-3-phenylpropanoate | 40203-94-9 | C11H11NO3 | 详情 | 详情 |
| (III) | 24397 | 5-amino-1,3,4-thiadiazole-2(3H)-thione | 2349-67-9 | C2H3N3S2 | 详情 | 详情 |
| (IV) | 38889 | methyl (2S)-3-phenyl-2-([[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino)propanoate | C13H14N4O3S2 | 详情 | 详情 |
Extended Information