NMI-1093
Chemical Name: 4-[5-(Nitrooxymethyl)-3-phenylisoxazol-4-yl]benzenesulfonamide
CAS No. 346683-70-3
项目整合开发状态: Preclinical
项目研究机构: NitroMed (Originator)
合成路线:Treatment of deoxybenzoin (I) with hydroxylamine hydrochloride produces the corresponding oxime (II).Condensation of the dilithium derivative of (II) with methyl chloroacetate (III) generates the dihydroisoxazole (IV).Subsequent chlorosulfonation of (IV),followed by treatment with ammonia,furnishes sulfonamide (V).Then,displacement of the chloro group of (V) with silver nitrate gives rise to the target nitrate ester.Alternatively,chloride (V) is converted to alcohol (VI) by displacement with formic acid,followed by alkaline hydrolysis.Then,reaction of alcohol (VI) with in situ generated acetyl nitrate yields the corresponding nitrate.
📌 参考资料/链接：
参考文献标题:Nitrosated and nitrosylated cyclooxygenase-2 inhibitors,compsns.and methods of use
文献作者:Garvey,D.S.; Tam,S.W.; Letts,L.G.; Schroeder,J.D.; Bandarage,U.K.; Fang,X.; Bandarage,R.R.(NitroMed Inc.)
参考来源:WO 0145703
📄 详细内容
合成路线:Treatment of deoxybenzoin (I) with hydroxylamine hydrochloride produces the corresponding oxime (II).Condensation of the dilithium derivative of (II) with methyl chloroacetate (III) generates the dihydroisoxazole (IV).Subsequent chlorosulfonation of (IV),followed by treatment with ammonia,furnishes sulfonamide (V).Then,displacement of the chloro group of (V) with silver nitrate gives rise to the target nitrate ester.Alternatively,chloride (V) is converted to alcohol (VI) by displacement with formic acid,followed by alkaline hydrolysis.Then,reaction of alcohol (VI) with in situ generated acetyl nitrate yields the corresponding nitrate.
参考文献标题:NMI-1093: A nitric oxide-enhanced cyclooxygenase-2 selective inhibitor with cardioprotective potential
文献作者:Schroeder,J.D.; et al.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 316
产品链接: CAS No. 346683-70-3››