MLN-944, XR-5944
Chemical Name: N,N'-(1,2-Ethanediy)bis(imino-2,1-ethanediyl)bis(9-methylphenazine-1-carboxamide)
CAS No. 206531-58-0 (monohydrochloride)
项目整合开发状态: Phase I
项目研究机构: Xenova (Originator), Millennium (Licensee)
合成路线:Copper-catalyzed coupling of o-toluidine (I) with 2-bromo-3-nitrobenzoic acid (II) gave the N-aryl-3-nitroanthranilic acid (III).Reductive cyclization with NaBH4 in the presence NaOEt produced the desired phenazine (V) along with amino anthranilic acid (VI),which were separated by fractional crystallization.Carboxylic acid (V) was then activated as the imidazolide (VI) upon treatment with carbonyl diimidazole.Finally,coupling of triethylenetetramine (VII) with two equivalents of imidazolide (VI) produced the title diamide.
📌 参考资料/链接：
参考文献标题:Bis(acridinecarboxamide) and bis(phenazinecarboxamide) as antitumour agents
文献作者:Denny,W.A.; Gamage,S.A.; Spicer,J.A.; Baguley,B.C.; Finlay,G.J.(Xenova Group plc)
参考来源:EP 0934278; GB 2334032; WO 9817650
📄 详细内容
合成路线:Copper-catalyzed coupling of o-toluidine (I) with 2-bromo-3-nitrobenzoic acid (II) gave the N-aryl-3-nitroanthranilic acid (III).Reductive cyclization with NaBH4 in the presence NaOEt produced the desired phenazine (V) along with amino anthranilic acid (VI),which were separated by fractional crystallization.Carboxylic acid (V) was then activated as the imidazolide (VI) upon treatment with carbonyl diimidazole.Finally,coupling of triethylenetetramine (VII) with two equivalents of imidazolide (VI) produced the title diamide.
参考文献标题:Potential antitumor agents.51.Synthesis and antitumor activity of substituted phenazine-1-carboxamides
文献作者:Rewcastle,G.W.; Denny,W.A.; Baguley,B.C.
参考来源:J Med Chem 1987,30(5),843