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

Kap Sun Yeung, 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

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)198-202
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Keywords

  • Amides
  • Antivirals
  • HIV-1 attachment inhibitors
  • Indole glyoxamide
  • Molecular conformation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Yeung, K. S., Qiu, Z., Xue, Q., Fang, H., Yang, Z., Zadjura, L., D'Arienzo, C. J., Eggers, B. J., Riccardi, K., Shi, P. Y., Gong, Y. F., Browning, M. R., Gao, Q., Hansel, S., Santone, K., Lin, P. F., Meanwell, N. A., & Kadow, J. F. (2013). Inhibitors of HIV-1 attachment. Part 7: Indole-7-carboxamides as potent and orally bioavailable antiviral agents. Bioorganic and Medicinal Chemistry Letters, 23(1), 198-202. https://doi.org/10.1016/j.bmcl.2012.10.115