CGP-64222

Chemical Name: N-(6-Aminohexyl)glycyl-[N-(3-guanidinopropyl)]glycyl-[N-(3-guanidinopropyl)]glycyl-(N-benzyl)glycyl-[N-(3-guanidinopropyl)]glycyl-D-lysyl-D-lysyl-D-arginyl-D-prolinamide
CAS No. 186380-62-1
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:The title compound was prepared by solid-phase peptide synthesis starting from N-Fmoc-D-proline linked to Rink resin (I).Deprotection of the Fmoc group by means of piperidine in DMA afforded proline-resin (II).Coupling of N-alpha-Fmoc-NG-Pmc-D-arginine (III) to proline-resin (II) using diisopropyl carbodiimide (DIC) and HOBt,followed by Fmoc deprotection with piperidine in DMA,furnished dipeptide-resin (IV).Further coupling and deprotection cycles incorporating the amino acid N2-Fmoc-N6-Boc-D-lysine (V) (twice) and the peptoid residue N-Fmoc-N-[3-(3-Pmc-guanidino)propyl]glycine (VIII) yielded the peptide resins (VI),(VII) and (IX),respectively.

合成路线:Further coupling and deprotection cycles incorporating peptoid N-Fmoc-N-benzylglycine (X),and twice peptoid (VIII),yielded the peptoid-resins (XI) and (XII),respectively.Bromoacetic acid (XIII) was subsequently coupled to resin (XII) to afford the bromoacetamido peptoid-resin (XIV).

合成路线:Displacement of the bromine of (XIV) with N-Boc-1,6-diaminohexane (XV) produced resin (XVI).Finally,the side-chain protecting groups of (XVI) were cleaved and the desired peptoid was liberated from the resin by treatment with trifluoroacetic acid.
📌 参考资料/链接:
参考文献标题:Antiviral peptoid cpds.
文献作者:Felder,E.; Hamy,F.; Heizmann,G.; Klimkait,T.; Lazdins,J.K.(Novartis AG)
参考来源:EP 0832110; WO 9640759

📄 详细内容


合成路线:The title compound was prepared by solid-phase peptide synthesis starting from N-Fmoc-D-proline linked to Rink resin (I).Deprotection of the Fmoc group by means of piperidine in DMA afforded proline-resin (II).Coupling of N-alpha-Fmoc-NG-Pmc-D-arginine (III) to proline-resin (II) using diisopropyl carbodiimide (DIC) and HOBt,followed by Fmoc deprotection with piperidine in DMA,furnished dipeptide-resin (IV).Further coupling and deprotection cycles incorporating the amino acid N2-Fmoc-N6-Boc-D-lysine (V) (twice) and the peptoid residue N-Fmoc-N-[3-(3-Pmc-guanidino)propyl]glycine (VIII) yielded the peptide resins (VI),(VII) and (IX),respectively.

合成路线:Further coupling and deprotection cycles incorporating peptoid N-Fmoc-N-benzylglycine (X),and twice peptoid (VIII),yielded the peptoid-resins (XI) and (XII),respectively.Bromoacetic acid (XIII) was subsequently coupled to resin (XII) to afford the bromoacetamido peptoid-resin (XIV).

合成路线:Displacement of the bromine of (XIV) with N-Boc-1,6-diaminohexane (XV) produced resin (XVI).Finally,the side-chain protecting groups of (XVI) were cleaved and the desired peptoid was liberated from the resin by treatment with trifluoroacetic acid.
参考文献标题:An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication
文献作者:Hamy,F.; Felder,E.R.; Heizmann,G.; Lazdins,J.; Aboul-ela,F.; Varani,G.; Karn,J.; Klimkait,T.
参考来源:Proceedings of the National Academy of Sciences of the United States of America 1997,94(8),3548


产品链接: CAS No. 186380-62-1››