DD-612
Chemical Name: N-[2-(1-Pyrrolidinyl)ethyl]-glycyl-N-cyclopropyl-glycyl-N2-(1-methylpropyl)glycinamide
项目整合开发状态: Preclinical
项目研究机构: DiverDrugs (Originator), Advancell (Licensee)
合成路线:The title compound is prepared by solid phase synthesis employing a Rink amide resin.Acylation of the resin with chloroacetyl chloride (I) affords the chloroacetyl resin (II).Subsequent chloride displacement with s-butylamine (III) provides the aminoacid-bound resin (IV).A new acylation of (IV) with chloroacetyl chloride (I) yields the chloroacetamide (V),which is then displaced by cyclopropylamine (VI),yielding the dipeptide derivative (VII).Then,a further coupling of (VII) with acid chloride (I),followed by displacement of the resultant chloroacetamide resin (VIII) with N-(2-aminoethyl)pyrrolidine (IX) gives rise to the tripeptide resin (X).Finally,cleavage of the dipeptide amide from the solid support is accomplished by treatment with trifluoroacetic acid in CH2Cl2
📌 参考资料/链接：
参考文献标题:N-Alkylglycine trimeres capable of protecting neurons against excitotoxic aggressions and compsns.containing said trimeres
文献作者:Felipo Orts,V.; Montoliu Felix,C.; Ferrer Montiel,A.; Planells Cases,R.; Merino Fernandez,J.M.; Perez Paya,E.; Sanchez Baeza,F.; Humet,M.; Messeguer Peypoch,A.(DiverDrugs SL)
参考来源:WO 0228885
📄 详细内容
合成路线:The title compound is prepared by solid phase synthesis employing a Rink amide resin.Acylation of the resin with chloroacetyl chloride (I) affords the chloroacetyl resin (II).Subsequent chloride displacement with s-butylamine (III) provides the aminoacid-bound resin (IV).A new acylation of (IV) with chloroacetyl chloride (I) yields the chloroacetamide (V),which is then displaced by cyclopropylamine (VI),yielding the dipeptide derivative (VII).Then,a further coupling of (VII) with acid chloride (I),followed by displacement of the resultant chloroacetamide resin (VIII) with N-(2-aminoethyl)pyrrolidine (IX) gives rise to the tripeptide resin (X).Finally,cleavage of the dipeptide amide from the solid support is accomplished by treatment with trifluoroacetic acid in CH2Cl2
参考文献标题:Prevention of in vivo excitotoxicity by a family of trialkylglycines,a novel class of neuroprotectants
文献作者:Montoliu,C.; Humet,M.; Canales,J.J.; Burda,J.; Planells-Cases,R.; Sanchez-Baeza,F.; Carbonell,T.; Perez-Paya,E.; Messeguer,A.; Ferrer-Montiel,A.; Felipo,V.
参考来源:J Pharm Exp Ther 2002,301(1),29