Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents

  • Bioorg Med Chem Lett. 2013 Jan 1;23(1):198-202. doi: 10.1016/j.bmcl.2012.10.115.
Kap-Sun Yeung  1 ,  Zhilei Qiu ,  Quifen Xue ,  Haiquan Fang ,  Zheng Yang ,  Lisa Zadjura ,  Celia J D'Arienzo ,  Betsy J Eggers ,  Keith Riccardi ,  Pei-Yong Shi ,  Yi-Fei Gong ,  Marc R Browning ,  Qi Gao ,  Steven Hansel ,  Kenneth Santone ,  Ping-Fang Lin ,  Nicholas A Meanwell ,  John F Kadow
Affiliations
  • 1. Bristol-Myers Squibb Research & Development, 5 Research Parkway, PO Box 5100, Wallingford, CT 06492, USA. [email protected]
PMID: 23200252 DOI: 10.1016/j.bmcl.2012.10.115
Abstract

A series of substituted carboxamides at the indole C7 position of the previously described 4-fluoro-substituted indole HIV-1 attachment inhibitor 1 was synthesized and the SAR delineated. Heteroaryl carboxamide inhibitors that exhibited pM potency in the primary cell-based assay against a pseudotype virus expressing a JRFL envelope were identified. The simple methyl amide analog 4 displayed a promising in vitro profile, with its favorable HLM stability and membrane permeability translating into favorable pharmacokinetic properties in preclinical species.