ANG-615
德尼布林Chemical Name: N-[5-[4-(L-Alanylamino)phenylsulfanyl]-1H-benzimidazol-2-yl]carbamic acid methyl ester
CAS No. 284019-34-7
项目整合开发状态: Preclinical
项目研究机构: Angiogene Pharmaceuticals (Originator)
合成路线:The reaction of 7-ethyl-10-hydroxycamptothecin (I) with phosgene gives 7-ethyl-10-(chlorocarbonyloxy)camptothecin (II),which is then condensed with 4-(1-piperidyl)piperidine.
合成路线:The condensation between 4-(acetylamino)thiophenol (I) and 5-chloro-2-nitroaniline (II) produced the diaryl sulfide (III).Nitro group reduction in (III) employing SnCl2 gave the phenylenediamine (IV),which was cyclized to the benzimidazole (VI) upon treatment with N,N'-bis(methoxycarbonyl)-S-methylisothiourea (V).Hydrolysis of the acetamido group of (VI) with HCl in MeOH afforded aniline (VII).This was acylated with N-Boc-alanine (VIII) in the presence of EDC to yield amide (IX).The N-Boc protecting group of (IX) was finally removed by treatment with trifluoroacetic acid.
📌 参考资料/链接：
参考文献标题:Benzimidazole vascular damaging agents
文献作者:Davis,P.D.(Angiogene Pharmaceuticals Ltd.)
参考来源:EP 1140078; WO 0041669
📄 详细内容
合成路线:The condensation between 4-(acetylamino)thiophenol (I) and 5-chloro-2-nitroaniline (II) produced the diaryl sulfide (III).Nitro group reduction in (III) employing SnCl2 gave the phenylenediamine (IV),which was cyclized to the benzimidazole (VI) upon treatment with N,N'-bis(methoxycarbonyl)-S-methylisothiourea (V).Hydrolysis of the acetamido group of (VI) with HCl in MeOH afforded aniline (VII).This was acylated with N-Boc-alanine (VIII) in the presence of EDC to yield amide (IX).The N-Boc protecting group of (IX) was finally removed by treatment with trifluoroacetic acid.
参考文献标题:Benzimidazole carbamates: A new structural class of vascular targeting agents
文献作者:Lewis,G.S.; Nolan,J.; Davis,P.D.; Naylor,M.A.; Thomson,P.; Hill,S.A.
参考来源:Proc Amer Assoc Cancer Res 2001,42Abst 2000
产品链接: CAS No. 284019-34-7››