CT-747
Chemical Name: N-[5,5-Dimethyl-3-(4-methylphenylsulfonyl)thiazolidin-4(R)-ylcarbonyl]-4-O-[3-(dimethylamino)propyl]-L-tyrosine
CAS No. 220397-12-6
项目整合开发状态: Preclinical
项目研究机构: Elan (Originator), Wyeth Pharmaceuticals (Originator)
合成路线:N-Boc-L-Tyrosine methyl ester (I) was alkylated with either 3-(dimethylamino)-1-propanol (II) under Mitsunobu conditions or with N,N-dimethyl-3-chloropropylamine (III) in the presence of K2CO3 to afford N-Boc-L-4-(3-dimethylaminopropoxy)phenylalanine methyl ester (IV).Subsequent acidic cleavage of the N-Boc protecting group of (IV) gave amino ester (V).N-Tosyl-L-5,5-dimethylthiaproline (VII) was obtained by treatment of L-5,5-dimethylthiaproline (VI) with p-toluenesulfonyl chloride in the presence of NaOH.Acid (VII) was then coupled to amino ester (V) using EDC and HOBt to furnish amide (VIII).Finally,basic hydrolysis of the methyl ester group of (VIII) yielded the title compound.
📌 参考资料/链接：
参考文献标题:Substd.phenylalanine type cpds.which inhibit leukocyte adhesion mediated by VLA-4
文献作者:Ashwell,S.; Konradi,A.W.; Lombardo,L.J.; Dappen,M.S.; Baudy,R.B.; Kreft,A.; Grant,F.S.; Sarantakis,D.; Pleiss,M.A.; Semko,C.M.; Dressen,D.B.; Thorsett,E.D.(American Home Products Corp.; Athena Neurosciences,Inc.)
参考来源:WO 9906431
📄 详细内容
合成路线:N-Boc-L-Tyrosine methyl ester (I) was alkylated with either 3-(dimethylamino)-1-propanol (II) under Mitsunobu conditions or with N,N-dimethyl-3-chloropropylamine (III) in the presence of K2CO3 to afford N-Boc-L-4-(3-dimethylaminopropoxy)phenylalanine methyl ester (IV).Subsequent acidic cleavage of the N-Boc protecting group of (IV) gave amino ester (V).N-Tosyl-L-5,5-dimethylthiaproline (VII) was obtained by treatment of L-5,5-dimethylthiaproline (VI) with p-toluenesulfonyl chloride in the presence of NaOH.Acid (VII) was then coupled to amino ester (V) using EDC and HOBt to furnish amide (VIII).Finally,basic hydrolysis of the methyl ester group of (VIII) yielded the title compound.
参考文献标题:CT747: A very potent and highly selective small molecule inhibitor of VLA4 that is metabolically stable
文献作者:Grant,F.S.; Dressen,D.B.; Dappen,M.S.; et al.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 135