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【结 构 式】 
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【药物名称】SA-6541 【化学名称】3-[4-(Dimethylamino)benzylsulfanyl]-2(R)-[2(S)-methyl-3-sulfanylpropionamido]propionic acid 【CA登记号】183121-23-5 【 分 子 式 】C16H24N2O3S2 【 分 子 量 】356.50928 |
【开发单位】Santen (Originator) 【药理作用】Antiarthritic Drugs, Antipsoriatics, DERMATOLOGIC DRUGS, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Leukotriene A4 Hydrolase Inhibitors |
合成路线1
The treatment of 4-(dimethylamino)benzyl alcohol (I) with concentrated HBr at 120 C in a sealed tube provided benzyl bromide (II). This was then condensed with N-Boc-L-cysteine (III) in the presence of N,N-diisopropyl ethylamine to furnish the benzyl thioether (IV). Subsequent cleavage of the Boc group of (IV) employing HCl in dioxan yielded the intermediate aminoacid (V).
| 【1】 Miyake, Y.; Horiuchi, M.; Mita, S.; Tsuji, F.; Involvement of leukotriene B4 in murine dermatitis models. Biochem Pharmacol 1998, 55, 297. |
| 【2】 Kawashima, Y.; Horiuchi, M. (Santen Pharmaceutical Co., Ltd.); Novel amino acid derivs. having N,N-dialkylaminophenyl group. EP 0870762; JP 1996301840; WO 9627585 . |
| 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) | 41579 | [4-(dimethylamino)phenyl]methanol | 1703-46-4 | C9H13NO | 详情 | 详情 |
| (II) | 41580 | 4-(bromomethyl)-N,N-dimethylaniline; N-[4-(bromomethyl)phenyl]-N,N-dimethylamine | C9H12BrN | 详情 | 详情 | |
| (III) | 20812 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid | 20887-95-0 | C8H15NO4S | 详情 | 详情 |
| (IV) | 41581 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid | C17H26N2O4S | 详情 | 详情 | |
| (V) | 41582 | (2R)-2-amino-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid | C12H18N2O2S | 详情 | 详情 |
合成路线2
(S)-3-Benzoylthio-2-methylpropionic acid (VI) was activated as the acid chloride (VII) by treatment with SOCl2 or optionally converted to the active ester (VIII) upon condensation with p-nitrophenol in the presence of DCC. Coupling of aminoacid (V) with either acid chloride (VII) under Schotten-Baumann conditions or with p-nitrophenyl ester (VIII) in the presence of Et3N gave rise to the corresponding amide (IX). The benzoyl thioester of (IX) was finally cleaved employing aqueous ammonia to afford the title thiol.
| 【1】 Miyake, Y.; Horiuchi, M.; Mita, S.; Tsuji, F.; Involvement of leukotriene B4 in murine dermatitis models. Biochem Pharmacol 1998, 55, 297. |
| 【2】 Kawashima, Y.; Horiuchi, M. (Santen Pharmaceutical Co., Ltd.); Novel amino acid derivs. having N,N-dialkylaminophenyl group. EP 0870762; JP 1996301840; WO 9627585 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 41582 | (2R)-2-amino-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid | C12H18N2O2S | 详情 | 详情 | |
| (VI) | 35379 | (2S)-3-(benzoylsulfanyl)-2-methylpropionic acid | C11H12O3S | 详情 | 详情 | |
| (VII) | 41584 | S-[(2R)-3-chloro-2-methyl-3-oxopropyl] benzenecarbothioate | C11H11ClO2S | 详情 | 详情 | |
| (VIII) | 35380 | 4-nitrophenyl (2S)-3-(benzoylsulfanyl)-2-methylpropanoate | C17H15NO5S | 详情 | 详情 | |
| (IX) | 41583 | (2R)-2-[[(2S)-3-(benzoylsulfanyl)-2-methylpropanoyl]amino]-3-[[4-(dimethylamino)benzyl]sulfanyl]propionic acid | C23H28N2O4S2 | 详情 | 详情 |