Discovery of novel (S)-alpha-phenyl-gamma-amino butanamide containing CCR5 antagonists via functionality inversion approach.
By using functionality inversion approach, we identified a new scaffold containing (S)-alpha-phenyl-gamma-amino butanamide as CCR5 antagonists derived from the 1,3-propanediamine carboxamide pharmacophore protocol. The (2S)-2-phenyl-4-(8-aza-bicyclo[3.2.1]octan-8-yl)-butanamide derivatives display significantly high potency to antagonize CCR5 receptor with nanomolar IC(50) values.
Zhang
Hu-Shan
HS
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, CAS, 555 Zuchongzhi Road, Shanghai 201203, China.
Feng
Dong-Zhi
DZ
Chen
Li
L
Long
Ya-Qiu
YQ
D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002073:Butanes / Q000737:chemistry / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D019713:Receptors, CCR5 / Q000378:metabolism*
D000577:Amides; D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5