MLN-576, XR-11576
Chemical Name: N-[2-(Dimethylamino)-1(R)-methylethyl]-4-methoxybenzo[a]phenazine-11-carboxamide
项目整合开发状态: Phase I
项目研究机构: Xenova (Originator), Millennium (Licensee)
合成路线:The oxidation of 5-methoxy-1-tetralone (I) with SeO2 gives 5-methoxy-1,2-naphthoquinone (II),which is cyclized with 2,3-diaminobenzoic acid (II) by means of HCl in refluxing ethanol to yield 4-methoxybenzo[a]phenazine-11-carboxylic acid (IV).Finally,this acid is converted into the target amide by its condensation with N1,N1,2(R)-trimethylethane-1,2-diamine (V) by means of CDI in DMF.
📌 参考资料/链接：
参考文献标题:Benzo[a]phenazin-11-carboxamide derivs.and their use as joint inhibitors of topomerase I and II
文献作者:Vicker,N.; Folkes,A.J.; Wang,S.; Milton,J.; Denny,W.A.(Xenova Group plc)
参考来源:WO 0146157
📄 详细内容
合成路线:The oxidation of 5-methoxy-1-tetralone (I) with SeO2 gives 5-methoxy-1,2-naphthoquinone (II),which is cyclized with 2,3-diaminobenzoic acid (II) by means of HCl in refluxing ethanol to yield 4-methoxybenzo[a]phenazine-11-carboxylic acid (IV).Finally,this acid is converted into the target amide by its condensation with N1,N1,2(R)-trimethylethane-1,2-diamine (V) by means of CDI in DMF.
合成路线:The intermediate chiral diamine (IV) (see Scheme no.28794701a,intermediate (V)) is prepared as follows: Reduction of N-Boc-D-alanine methyl ester (I) with DIBAL affords N-Boc-alaninal (II),which is reductively aminated with dimethylamine in the presence of NaBH3CN to afford the Boc-protected diamine (III).The N-Boc group of (III) is finally removed under acidic conditions to provide the target (R)-diamine (IV).
参考文献标题:Novel angular benzophenazines: Dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents
文献作者:Vicker,N.; Burgess,L.; Chuckowree,I.S.; Dodd,R.; Folkes,A.J.; Hardick,D.J.; Hancox,T.C.; Miller,W.H.; Milton,J.; Sohal,S.; Wang,S.; Wren,S.P.; Charlton,P.A.; Dangerfield,W.; Liddle,C.; Mistry,P.; Stewart,A.J.; Denny,W.A.
参考来源:J Med Chem 2002,45(3),721