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【结 构 式】 
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【药物名称】Tanomastat, BAY-12-9566 【化学名称】4-(4'-Chlorobiphenyl-4-yl)-4-oxo-2(S)-(phenylsulfanylmethyl)butyric acid 【CA登记号】179545-77-8, 215258-80-3 (error in CA), 179545-78-9 (R-isomer), 179545-76-7 (undefined isomer) 【 分 子 式 】C23H19ClO3S 【 分 子 量 】410.92308 |
【开发单位】Bayer (Originator) 【药理作用】Antiarthritic Drugs, IMMUNOMODULATING AGENTS, ONCOLYTIC DRUGS, Osteoarthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Transplant Rejection, Angiogenesis Inhibitors, MMP-2 (Gelatinase A) Inhibitors, MMP-3 (Stromelysin 1) Inhibitors, MMP-9 (Gelatinase B) Inhibitors |
合成路线1
The Friedel-Crafts condensation of 4-chlorobiphenyl (I) with 3-methylenetetrahydrofuran-2,5-dione (II) by means of AlCl3 in tetrachloroethane gives 4-(4'-chlorobiphenyl-4-yl)-2-methylene-4-oxobutyric acid (III), which is treated with thiophenol (IV) and K2CO3 in DMF/water, yielding racemic 4-(4'-chlorobiphenyl-4-yl)-4-oxo-2-(phenylsulfanylmethyl)butyric acid (V). Finally, racemic (V) is resolved by means of crystallization with (+)-cinchonine in acetone.
| 【1】 Sorbera, L.A.; Castañer, J.; Graul, A.; Silvestre, J.S.; Bay-12-9566. Drugs Fut 1999, 24, 1, 16. |
| 【2】 Kluender, H.C.E.; Benz, G.H.H.H.; Brittelli, D.R.; Bullock, W.H.; Combs, K.J.; Dixon, B.R.; Schneider, S.; Wood, J.E.; Vanzandt, M.C.; Wolanin, D.J.; Wilhelm, S.M. (Bayer AG); Substd. 4-biarylbutyric or 5-biarylpentanoic acids and derivs. as matrix metalloprotease inhibitors. EP 0790974; JP 1998509146; US 5789434; US 5859047; WO 9615096 . |
| 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) | 20252 | 4-chloro-1,1'-biphenyl | 2051-62-9 | C12H9Cl | 详情 | 详情 |
| (II) | 12891 | 3-Methylenedihydro-2,5-furandione; Itaconic anhydride | 2170-03-8 | C5H4O3 | 详情 | 详情 |
| (III) | 20254 | 2-[2-(4'-chloro[1,1'-biphenyl]-4-yl)-2-oxoethyl]acrylic acid | C17H13ClO3 | 详情 | 详情 | |
| (IV) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (V) | 20256 | 4-(4'-chloro[1,1'-biphenyl]-4-yl)-4-oxo-2-[(phenylsulfanyl)methyl]butyric acid | C23H19ClO3S | 详情 | 详情 |