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

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

Affiliation

  • 1 Bristol-Myers Squibb Research & Development, 5 Research Parkway, PO Box 5100, Wallingford, CT 06492, USA. kapsun.yeung@bms.com
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.

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