新产品编号:736139
Chemical Name: 3(R)-[3'-[3-(1H-Benzimidazol-2-yl)ureido]-4-methoxybiphenyl-3-ylsulfonamido]-3-phenylpropionic acid
CAS No. 276261-99-5, 276259-37-1 (racemate)
项目整合开发状态: Biological Testing
项目研究机构: Bayer (Originator)
合成路线:The title compound was synthesized within a combinatorial library on a Wang polystyrene resin.Attachment of N-Fmoc-(R)-beta-phenylalanine (I) to the solid support was achieved via activation with 2,6-dichlorobenzoyl chloride to afford the aminoacid-bound resin (II).After conventional Fmoc group deprotection with piperidine in DMF,the resultant amine resin (III) was acylated with 5-bromo-2-methoxybenzenesulfonyl chloride (IV) yielding sulfonamide (V).Mitsunobu coupling between aryl bromide (V) and 3-nitrobenzeneboronic acid (VI) gave rise to the biphenyl derivative (VII).Reduction of the nitro group of (VII) to the corresponding aniline (VIII) was then performed by treatment with stannous chloride in N-methylpyrrolidone.Alternatively,the aminobiphenyl resin (VIII) was directly prepared by coupling between aryl bromide (V) and 3-aminobenzeneboronic acid (IX).Reaction of amine (VIII) with p-nitrophenyl chloroformate (X) produced the nitrophenyl carbamate resin (IX),which was further reacted with 2-aminobenzimidazole (XII) to furnish urea (XIII).Final resin cleavage was effected by treatment with trifluoroacetic acid in CH2Cl2.
📌 参考资料/链接：
参考文献标题:New biphenyl and biphenyl-analogous cpds.as integrin antagonists
文献作者:Schmidt,D.; Urbahns,K.; Gerdes,C.; Keldenich,J.; H鋜ter,M.; Stahl,E.; Albers,M.; Vaupel,A.; Stelte-Ludwig,B.; Br黦gemeier,U.; Lustig,K.(Bayer AG)
参考来源:EP 1140809; JP 2002532465; US 6420396; WO 0035864
📄 详细内容
合成路线:The title compound was synthesized within a combinatorial library on a Wang polystyrene resin.Attachment of N-Fmoc-(R)-beta-phenylalanine (I) to the solid support was achieved via activation with 2,6-dichlorobenzoyl chloride to afford the aminoacid-bound resin (II).After conventional Fmoc group deprotection with piperidine in DMF,the resultant amine resin (III) was acylated with 5-bromo-2-methoxybenzenesulfonyl chloride (IV) yielding sulfonamide (V).Mitsunobu coupling between aryl bromide (V) and 3-nitrobenzeneboronic acid (VI) gave rise to the biphenyl derivative (VII).Reduction of the nitro group of (VII) to the corresponding aniline (VIII) was then performed by treatment with stannous chloride in N-methylpyrrolidone.Alternatively,the aminobiphenyl resin (VIII) was directly prepared by coupling between aryl bromide (V) and 3-aminobenzeneboronic acid (IX).Reaction of amine (VIII) with p-nitrophenyl chloroformate (X) produced the nitrophenyl carbamate resin (IX),which was further reacted with 2-aminobenzimidazole (XII) to furnish urea (XIII).Final resin cleavage was effected by treatment with trifluoroacetic acid in CH2Cl2.
参考文献标题:Biphenyls as potent vitronectin receptor antagonists
文献作者:Urbahns,K.; H鋜ter,M.; Albers,M.; Schmidt,D.; Stelte-Ludwig,B.; Br黦gemeier,U.; Vaupel,A.; Gerdes,C.
参考来源:Bioorg Med Chem Lett 2002,12(2),205