title: Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents.
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.
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, PO Box 5100, Wallingford, CT 06492, USA. kapsun.yeung@bms.com
authors.forename: Kap-Sun
authors.initials: KS
authors.lastname: Yeung
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Qiu
authors.forename: Quifen
authors.initials: Q
authors.lastname: Xue
authors.forename: Haiquan
authors.initials: H
authors.lastname: Fang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Lisa
authors.initials: L
authors.lastname: Zadjura
authors.forename: Celia J
authors.initials: CJ
authors.lastname: D'Arienzo
authors.forename: Betsy J
authors.initials: BJ
authors.lastname: Eggers
authors.forename: Keith
authors.initials: K
authors.lastname: Riccardi
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Gong
authors.forename: Marc R
authors.initials: MR
authors.lastname: Browning
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Steven
authors.initials: S
authors.lastname: Hansel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Santone
authors.forename: Ping-Fang
authors.initials: PF
authors.lastname: Lin
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.forename: John F
authors.initials: JF
authors.lastname: Kadow
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D018360:Crystallography, X-Ray; D004285:Dogs; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D053585:Virus Attachment / Q000187:drug effects
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D007211:Indoles; C030374:indole