新产品编号:1085761
Chemical Name: 8(S)-(Bromomethyl)-6-(4-methoxycinnamoyl)-2-methyl-4-[N-(4-methylpiperazin-1-yl)carbamoyloxy]-3,6,7,8-tetrahydrobenzo[1,2,b:4,3-b']dipyrrole-1-carboxylic acid methyl ester hydrobromide
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-methylpiperazine-1-amine (VIII),and treated with HBr to furnish the target dihydrobromide.
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-(1-piperidinyl)piperidine-1-amine (VIII),and treated with HBr to furnish the target hydrobromide.
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-methylpiperazine-1-amine (VIII),and treated with HBr to furnish the target hydrobromide.
📌 参考资料/链接：
参考文献标题:DC-89 deriv.
文献作者:Amishiro,N.; Nagamura,S.; Saito,H.; Kobayashi,E.; Okamoto,A.; Gomi,K.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 0702014; US 5670492; WO 9526964
📄 详细内容
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-methylpiperazine-1-amine (VIII),and treated with HBr to furnish the target dihydrobromide.
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-(1-piperidinyl)piperidine-1-amine (VIII),and treated with HBr to furnish the target hydrobromide.
合成路线:The hydrolysis of DU-86 (I) with NaOMe gives tetracyclic compound (II),which is acylated with the 4-nitrophenyl cinnamate (III) and NaH yielding the adduct (IV).The opening of the cyclopropane ring of (IV) with HBr in acetonitrile affords the aromatic phenol (V),which is activated with 4-nitrophenyl chloroformate (VI) and TEA to provide the activated anhydride (VII).Finally,this compound is condensed with 4-methylpiperazine-1-amine (VIII),and treated with HBr to furnish the target hydrobromide.
参考文献标题:Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups
文献作者:Amishiro,N.; Nagamura,S.; Murakata,C.; Okamoto,A.; Kobayashi,E.; Asada,M.; Gomi,K.; Tamaoki,T.; Okabe,M.; Yamaguchi,N.; Yamaguchi,K.; Saito,H.
参考来源:Bioorg Med Chem 2000,8(2),381