NCX-530
Chemical Name: 2-[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid 3-(nitrooxymethyl)phenyl ester
CAS No. 204268-63-3
项目整合开发状态: Preclinical
项目研究机构: NicOx (Originator), Kyoto Pharmaceutical University (Codevelopment)
合成路线:The title compound was synthesized by two procedures.Indomethacin (I) was coupled with 3-hydroxybenzyl nitrate (II) using DCC to yield the title ester.
📌 参考资料/链接：
参考文献标题:Nitric ester derivs.and their use in urinary incontinence and other diseases
文献作者:Del Soldato,P.; Sannicolo',F.(NicOx SA)
参考来源:JP 2000517332; WO 9809948
📄 详细内容
合成路线:Alternatively,coupling of 3-hydroxybenzaldehyde (I) with acetylsalicyloyl chloride (II) by means of Et3N in dichloromethane affords 2-acetoxybenzoic acid 3-formyl-phenyl ester (IV),which is then reduced by hydrogenation over Pd/C in ethyl acetate to provide alcohol (III).Chlorination of alcohol (III) by treatment with thionyl chloride in DMF gives the chloromethyl derivative (V),which is finally converted to NCX-4016 by treatment with AgNO3 in refluxing acetonitrile.
合成路线:In a related procedure,indomethacin chloride (III) was coupled with 3-hydroxybenzaldehyde (IV) to yield ester (V).Catalytic hydrogenation of the formyl group of (V) over Pd/C produced alcohol (VI),which was further converted to chloride (VII) upon treatment with SOCl2.The chloride group of (VII) was finally displaced with silver nitrate to furnish the corresponding nitrate ester.
参考文献标题:Synthesis method of nitroxymethylphenyl esters of aspirin derivs.
文献作者:Garufi,M.; Del Soldato,P.(NicOx SA)
参考来源:WO 0044705