PD-176078
Chemical Name: N-[4,4-Bis(4-fluorophenyl)butyl]-4-methyl-2(S)-(methylamino)pentanamide hydrochloride; N1-[4,4-Bis(4-fluorophenyl)butyl]-N2-methyl-L-leucinamide hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Condensation of 4,4-bis(4-fluorophenyl)butyl bromide (I) with potassium phthalimide (II) in hot DMF yielded the substituted phthalimide (III).Deprotection of the phthalimido group of (III) to give primary amine (IV) was effected by treatment with NaBH4,followed by methanolic HCl.Subsequent coupling of (IV) with N-Boc-N-methyl-L-leucine (V) by means of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate furnished amide (VI).Finally,the Boc group of (VI) was deprotected using trifluoroacetic acid in CH2Cl2 and treated with HCl.
📌 参考资料/链接：
参考文献标题:Substd.diarylalkyl amides as calcium channel antagonists
文献作者:Song,Y.; Rafferty,M.F.; Ryder,T.R.; Sercel,A.D.; Connor,D.T.; Malone,T.C.; Hu,L.-Y.; Roth,B.D.(Pfizer Inc.)
参考来源:WO 9955688
📄 详细内容
合成路线:Condensation of 4,4-bis(4-fluorophenyl)butyl bromide (I) with potassium phthalimide (II) in hot DMF yielded the substituted phthalimide (III).Deprotection of the phthalimido group of (III) to give primary amine (IV) was effected by treatment with NaBH4,followed by methanolic HCl.Subsequent coupling of (IV) with N-Boc-N-methyl-L-leucine (V) by means of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate furnished amide (VI).Finally,the Boc group of (VI) was deprotected using trifluoroacetic acid in CH2Cl2 and treated with HCl.
参考文献标题:(S)-4-methyl-2-(methylamino)pentanoic acid [4,4-bis(4-fluorophenyl)butyl]amide hydrochloride,a novel calcium channel antagonist,is efficacious in several animal models of pain
文献作者:Song,Y.; Bowersox,S.S.; Connor,D.T.; Dooley,D.J.; Lotarski,S.M.; Malone,T.; Miljanich,G.P.; Millerman,E.; Rafferty,M.F.; Rock,D.M.; Roth,B.D.; Schmidt,J.; Stoehr,S.; Szoke,B.G.; Taylor,C.P.; Vartanian,M.G.; Wang,Y.X.
参考来源:J Med Chem 2000,43(19),3474