Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly potent Anti-HIV-1 activity

…, Y Nishikawa, N Kanzaki, K Takashima…

Index: Imamura, Shinichi; Ichikawa, Takashi; Nishikawa, Youichi; Kanzaki, Naoyuki; Takashima, Katsunori; Niwa, Shinichi; Iizawa, Yuji; Baba, Masanori; Sugihara, Yoshihiro Journal of Medicinal Chemistry, 2006 , vol. 49, # 9 p. 2784 - 2793

Full Text: HTML

Citation Number: 59

Abstract

We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated membrane fusion (IC50= 5.8 nM). Further ...