新产品编号:1161697
Chemical Name: 2(S)-(Benzyloxycarbonylamino)-3-[2-[4(S)-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]-2,5-dioxoimidazolidin-1-yl]acetamido]propionic acid
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator)
合成路线:Conversion of amino acid (I) into its methyl ester derivative (II) by means of SOCl2 in MeOH,followed by coupling with ethyl isocyanatoacetate (III) and Et3N in CH2Cl2/THF yields derivative (IV).Cyclization of (IV) by means of H2O/HCl affords hydantoin (V),which reacts with 2-methylthio-2-imidazoline (VI) in an aqueous NaOH solution to provide cyclic guanidine derivative (VII).Treatment of amino acid (VIII) with isobutylene (IX) and H2SO4 in dioxane affords t-Bu ester (X),which then couples with (VII) by means of HOBt and DCC in DMF to furnish derivative (XI).Finally,tert-butyl ester is hydrolyzed by treatment with TFA in the presence of 1,2-dimercaptoethane.
📌 参考资料/链接：
参考文献标题:Inhibitors of bone resorption and vitronectin receptor antagonists
文献作者:Wehner,V.; Knolle,J.; Stilz,H.U.; Carniato,D.; Gourvest,J.-F.; Gadek,T.; McDowell,R.(Aventis SA)
参考来源:DE 19626701; DE 19635522; EP 0796855
📄 详细内容
合成路线:Conversion of amino acid (I) into its methyl ester derivative (II) by means of SOCl2 in MeOH,followed by coupling with ethyl isocyanatoacetate (III) and Et3N in CH2Cl2/THF yields derivative (IV).Cyclization of (IV) by means of H2O/HCl affords hydantoin (V),which reacts with 2-methylthio-2-imidazoline (VI) in an aqueous NaOH solution to provide cyclic guanidine derivative (VII).Treatment of amino acid (VIII) with isobutylene (IX) and H2SO4 in dioxane affords t-Bu ester (X),which then couples with (VII) by means of HOBt and DCC in DMF to furnish derivative (XI).Finally,tert-butyl ester is hydrolyzed by treatment with TFA in the presence of 1,2-dimercaptoethane.
参考文献标题:RGD mimetics containing a central hydantoin scaffold: alphavbeta3 vs alphaIIbbeta3 selective requirements
文献作者:Peyman,A.; Wehner,V.; Knolle,J.; Stilz,H.U.; Breipohl,G.; Scheunemann,K.H.; Carniato,D.; Ruxer,J.M.; Gourvest,J.F.; Gadek,T.R.; Bodary,S.
参考来源:Bioorg Med Chem Lett 2000,10(2),179