BIO-1211
Chemical Name: N-[4-[3-(2-Methylphenyl)ureido]phenylacetyl]-L-leucyl-L-aspartyl-L-valyl-L-proline
CAS No. 187735-94-0
项目整合开发状态: Phase II
项目研究机构: Biogen Idec (Originator), Merck & Co. (Codevelopment)
合成路线:N-Boc-L-Valine N-hydroxysuccinimidyl ester (I) was coupled to L-proline benzyl ester (II),and the resulting Boc dipeptide (III) was subsequently deprotected with trifluoroacetic acid in CH2Cl2 to afford (IV).This was condensed with N-Boc-L-aspartic acid gamma-benzyl 1-N-hydroxysuccinimidyl diester (V) to give (VI).After Boc deprotection of (VI) with trifluoroacetic acid,tripeptide (VII) was coupled with N-Boc-L-leucine N-hydroxysuccinimidyl ester (VIII) to yield tetrapeptide (IX).Further Boc deprotection of (IX) with trifluoroacetic acid furnished peptide intermediate (X).
合成路线:Condensation of o-tolyl isocyanate (XI) with 4-aminophenylacetic acid (XII) produced urea (XIII).This was coupled to tetrapeptide (X) using EDC and HOBt to give the corresponding amide (XIV).Finally,the benzyl ester groups of (XIV) were deprotected by hydrogenolysis over Pd/C.
📌 参考资料/链接：
参考文献标题:Cell adhesion inhibitor
文献作者:Lin,K.-C.; Adams,S.P.; Castro,A.C.; Zimmerman,C.N.; Cuervo,J.H.; Lee,W.-C.; Hammond,C.E.; Carter,M.B.; Almquist,R.G.; Ensinger,C.L.(Biogen,Inc.)
参考来源:EP 0842196; JP 1999511124; WO 9703094
📄 详细内容
合成路线:N-Boc-L-Valine N-hydroxysuccinimidyl ester (I) was coupled to L-proline benzyl ester (II),and the resulting Boc dipeptide (III) was subsequently deprotected with trifluoroacetic acid in CH2Cl2 to afford (IV).This was condensed with N-Boc-L-aspartic acid gamma-benzyl 1-N-hydroxysuccinimidyl diester (V) to give (VI).After Boc deprotection of (VI) with trifluoroacetic acid,tripeptide (VII) was coupled with N-Boc-L-leucine N-hydroxysuccinimidyl ester (VIII) to yield tetrapeptide (IX).Further Boc deprotection of (IX) with trifluoroacetic acid furnished peptide intermediate (X).
合成路线:Condensation of o-tolyl isocyanate (XI) with 4-aminophenylacetic acid (XII) produced urea (XIII).This was coupled to tetrapeptide (X) using EDC and HOBt to give the corresponding amide (XIV).Finally,the benzyl ester groups of (XIV) were deprotected by hydrogenolysis over Pd/C.
参考文献标题:Selective,tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses
文献作者:Lin,K.; Ateeq,H.S.; Hsiung,S.H.; Chong,L.T.; Zimmerman,C.N.; Castro,A.; Lee,W.C.; Hammond,C.E.; Kalkunte,S.; Chen,L.L.; Pepinsky,R.B.; Leone,D.R.; Sprague,A.G.; Abraham,W.M.; Gill,A.; Lobb,R.R.; Adams,S.P.
参考来源:J Med Chem 1999,42(5),920
产品链接: CAS No. 187735-94-0››