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

30 Citations (Scopus)

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

Fingerprint

Antiviral Agents
HIV-1
Pharmacokinetics
Viruses
Amides
Permeability
Assays
Membranes
indole
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

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

Cite this

Inhibitors of HIV-1 attachment. Part 7 : Indole-7-carboxamides as potent and orally bioavailable antiviral agents. / Yeung, Kap Sun; Qiu, Zhilei; Xue, Quifen; Fang, Haiquan; Yang, Zheng; Zadjura, Lisa; D'Arienzo, Celia J.; Eggers, Betsy J.; Riccardi, Keith; Shi, Pei-Yong; Gong, Yi Fei; Browning, Marc R.; Gao, Qi; Hansel, Steven; Santone, Kenneth; Lin, Ping Fang; Meanwell, Nicholas A.; Kadow, John F.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 1, 01.01.2013, p. 198-202.

Research output: Contribution to journalArticle

Yeung, KS, Qiu, Z, Xue, Q, Fang, H, Yang, Z, Zadjura, L, D'Arienzo, CJ, Eggers, BJ, Riccardi, K, Shi, P-Y, Gong, YF, Browning, MR, Gao, Q, Hansel, S, Santone, K, Lin, PF, Meanwell, NA & Kadow, JF 2013, 'Inhibitors of HIV-1 attachment. Part 7: Indole-7-carboxamides as potent and orally bioavailable antiviral agents', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 1, pp. 198-202. https://doi.org/10.1016/j.bmcl.2012.10.115
Yeung, Kap Sun ; Qiu, Zhilei ; Xue, Quifen ; Fang, Haiquan ; Yang, Zheng ; Zadjura, Lisa ; D'Arienzo, Celia J. ; Eggers, Betsy J. ; Riccardi, Keith ; Shi, Pei-Yong ; Gong, Yi Fei ; Browning, Marc R. ; Gao, Qi ; Hansel, Steven ; Santone, Kenneth ; Lin, Ping Fang ; Meanwell, Nicholas A. ; Kadow, John F. / Inhibitors of HIV-1 attachment. Part 7 : Indole-7-carboxamides as potent and orally bioavailable antiviral agents. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 1. pp. 198-202.
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