PD-176078-药物合成数据库

【药物名称】PD-176078

化学结构式(Chemical Structure):

参考文献No.	41041
标题:	Substd. diarylalkyl amides as calcium channel antagonists
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.)
来源:	WO 9955688

合成路线图解说明: 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No.	593572
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
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.
来源:	J Med Chem 2000,43(19),3474

合成路线图解说明: 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.