KSG-504
4-{[N-乙酰基-N-(2,6-二甲基苯基)-β-丙氨酰](2-乙基-6-甲基苯基)氨基}丁酸Chemical Name: 4(R)-[N-(3-Methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulfonyl)pentanoic acid L-arginine salt monohydrate
CAS No. 137005-17-5 (anhydrous), 137004-84-3 (free acid)
项目整合开发状态: Phase I
项目研究机构: Kissei (Originator)
合成路线:The reaction of 2-naphthalenethiol (I) with 2-methyleneglutaronitrile (II) followed by treatment first with concentrated hydrochloric acid and then with p-toluenesulfonic acid in methanol gives racemic acid,which is resolved into optically pure (R)-4-methoxycarbonyl-2-(2-naphthylthiomethyl)butyric acid (IV) by use of (R)-(+)-alpha-methylbenzylamine (III).The treatment of compound (IV),first with thionyl chloride and then with N-(3-methoxypropyl)-N-pentylamine (V),affords (R)-methyl 4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylthio)pentanoate (VI).Oxidation of compound (VI) with m-chloroperbenzoic acid followed by treatment with 1N sodium hydroxide gives (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoic acid (VII),which is finally converted into KSG-504 by treatment with L-arginine.
📌 参考资料/链接：
参考文献标题:Napthylsulfonylalkanoic acid cpds
文献作者:Kitazawa,M.; Akahane,M.; Nakano,Y.; Tsubaki,A.; Sato,K.; Ban,M.; Kobayashi,M.(Kissei Pharmaceutical Co.,Ltd.)
参考来源:EP 0433064; JP 1991193756; JP 1991197453; JP 1992210956; US 5177069
📄 详细内容
合成路线:The reaction of 2-naphthalenethiol (I) with 2-methyleneglutaronitrile (II) followed by treatment first with concentrated hydrochloric acid and then with p-toluenesulfonic acid in methanol gives racemic acid,which is resolved into optically pure (R)-4-methoxycarbonyl-2-(2-naphthylthiomethyl)butyric acid (IV) by use of (R)-(+)-alpha-methylbenzylamine (III).The treatment of compound (IV),first with thionyl chloride and then with N-(3-methoxypropyl)-N-pentylamine (V),affords (R)-methyl 4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylthio)pentanoate (VI).Oxidation of compound (VI) with m-chloroperbenzoic acid followed by treatment with 1N sodium hydroxide gives (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoic acid (VII),which is finally converted into KSG-504 by treatment with L-arginine.
参考文献标题:KSG-504
文献作者:Kitazawa,M.; Akahane,M.; Yamazaki,Y.; Kobayashi,M.
参考来源:Drugs Fut 1995,20(5),472
产品链接: CAS No. 137005-17-5››