title: Inhibitors of HIV-1 attachment. Part 10. The discovery and structure-activity relationships of 4-azaindole cores.
abstract: A series of 4-azaindole oxoacetic acid piperazine benzamides was synthesized and evaluated in an effort to identify an oral HIV-1 attachment inhibitor with the potential to improve upon the pre-clinical profile of BMS-378806 (7), an initial clinical compound. Modifications at the 7-position of the 4-azaindole core modulated potency significantly and SAR showed that certain compounds with a 5-membered ring heteroaryl group at that position were the most potent. Four of the compounds with the best profiles were evaluated in a rat pharmacokinetic model and all had superior oral bioavailability and lower clearance when compared with 7.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Gong
authors.forename: Keith A
authors.initials: KA
authors.lastname: Riccardi
authors.forename: Pin-Fang
authors.initials: PF
authors.lastname: Lin
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Parker
authors.forename: Sandhya
authors.initials: S
authors.lastname: Rahematpura
authors.forename: Marina
authors.initials: M
authors.lastname: Mathew
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
authors.forename: John F
authors.initials: JF
authors.lastname: Kadow
authors.forename: John A
authors.initials: JA
authors.lastname: Bender
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D053585:Virus Attachment / Q000187:drug effects
chemical_list: C522780:4-azaindole; D019380:Anti-HIV Agents; C477855:BMS-378806; D007211:Indoles; D010879:Piperazines