DB-289

4,4'-(2,5-呋喃基)双[N-甲氧基苯甲脒]Chemical Name: 4,4'-(Furan-2,5-diyl)bis(N-methoxybenzamidine)
CAS No. 186953-56-0
项目整合开发状态: Phase II
项目研究机构: MediChem (Supplier), Georgia State University (Originator), University of North Carolina (Originator), Immtech (Licensee), CombinatoRx (Codevelopment)
合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V),which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.
📌 参考资料/链接:
参考文献标题:Furan derivs.for inhibiting Pneumocystis carinii pneumonia,Giardia lamblia and Cryptosporidium parvum
文献作者:Tidwell,R.R.; Hall,J.E.; Kumar,A.; Dykstra,C.C.; Boykin,D.W.; Wilson,W.D.; Blagburn,B.L.(Auburn University; Georgia State University; University of North Carolina)
参考来源:WO 9615126

📄 详细内容


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V),which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.

合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

参考文献标题:Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs
文献作者:Boykin,D.W.; et al.
参考来源:Bioorg Med Chem Lett 1996,6(24),3017


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V),which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.

合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

参考文献标题:2,5-Bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents
文献作者:Boykin,D.W.; Kumar,A.; Xiao,G.; Wilson,W.D.; Bender,B.C.; McCurdy,D.R.; Hall,J.E.; Tidwell,R.R.
参考来源:J Med Chem 1998,41(1),124


合成路线:The reaction of furan (I) with BuLi and Bu3Sn-Cl gives the bis tributyltin derivative (II),which is condensed with 4-bromobenzonitrile (III) by means of Pd(PPh3)4 in dioxane to yield 4,4'-(furan-2,5-diyl)-bis(benzonitrile) (IV).The reaction of (IV) with HCl and ethanol affords 4,4'-(furan-2,5-diyl)bis(ethyl benzimidate) (V),which is finally treated with O-methylhydroxylamine in ethanol to provide the target bis-O-methyl benzamidoxime.
参考文献标题:Synthesis,characterization,and formulation of DB289,a novel dication prodrug for the treatment of African sleeping sickness and Pneumocystis carinii pneumonia (PCP)
文献作者:McChesney-Harris,L.; et al.
参考来源:41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001,Chicago) 2001,Abst F-2162


产品链接: CAS No. 186953-56-0››