AZD-6126, ZD-6126, ANG-453
N-[(5S)-6,7-二氢-9,10,11-三甲氧基-3-(磷酰氧基)-5H-二苯并[a,c]环庚烯-5-基]乙酰胺Chemical Name: 5(S)-Acetamido-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl dihydrogen phosphate
CAS No. 219923-05-4
项目整合开发状态: Preclinical
项目研究机构: Angiogene Pharmaceuticals (Originator), AstraZeneca (Licensee)
合成路线:The title phosphate ester was prepared from N-acetylcolchinol (I).Treatment of (I) with di-tert-butyl diethylphosphoramidite in the presence of tetrazole provided the phosphite ester (II),which was subsequently oxidized to phosphate (III) by means of MCPBA.The tert-butyl phosphate ester of (III) was finally cleaved using trifluoroacetic acid.
📌 参考资料/链接：
参考文献标题:Use of colchinol derivs.as vascular damaging agents
文献作者:Dougherty,G.(Angiogene Pharmaceuticals Ltd.)
参考来源:WO 9902166
📄 详细内容
合成路线:The reaction of colchicin (I) with aq.HCl at 100 C gives the monodemethylated compound (II),which is treated with H2O2 at 60 C to yield the dibenzocycloheptene derivative (III).The condensation of (III) with N,N-diethylphosphoramidic acid di-tert-butyl ester (IV) by means of tetrazole affords the phosphoric acid triester (V),which is finally treated with MCPBA to provide the target phosphoric acid monoester.
参考文献标题:ZD6126: A novel vascular-targeting agent that causes selective destruction of tumor vasculature
文献作者:Davis,P.D.; Dougherty,G.J.; Blakey,D.C.; Galbraith,S.M.; Tozer,G.M.; Holder,A.L.; Naylor,M.A.; Nolan,J.; Stratford,M.R.; Chaplin,D.J.; Hill,S.A.
参考来源:Cancer Res 2002,62(24),7247
产品链接: CAS No. 219923-05-4››