title: Azaindole hydroxamic acids are potent HIV-1 integrase inhibitors.
abstract: HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication. Recently, HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Herein, we report the discovery of azaindole carboxylic acids and azaindole hydroxamic acids as potent inhibitors of the HIV-1 IN enzyme and their structure-activity relationships. Several 4-fluorobenzyl substituted azaindole hydroxamic acids showed potent antiviral activities in cell-based assays and offered a structurally simple scaffold for the development of novel HIV-1 IN inhibitors.
authors.affiliation: Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, California 92121, USA. michael.plewe@pfizer.com
authors.forename: Michael B
authors.initials: MB
authors.lastname: Plewe
authors.forename: Scott L
authors.initials: SL
authors.lastname: Butler
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Dress
authors.forename: Qiyue
authors.initials: Q
authors.lastname: Hu
authors.forename: Ted W
authors.initials: TW
authors.lastname: Johnson
authors.forename: Jon E
authors.initials: JE
authors.lastname: Kuehler
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuki
authors.forename: Hieu
authors.initials: H
authors.lastname: Lam
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Dawn
authors.initials: D
authors.lastname: Nowlin
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Peng
authors.forename: Sadayappan V
authors.initials: SV
authors.lastname: Rahavendran
authors.forename: Steven P
authors.initials: SP
authors.lastname: Tanis
authors.forename: Khanh T
authors.initials: KT
authors.lastname: Tran
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Anle
authors.initials: A
authors.lastname: Yang
authors.forename: Junhu
authors.initials: J
authors.lastname: Zhang
mesh_terms: D004353:Drug Evaluation, Preclinical; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008274:Magnesium / Q000378:metabolism; D010847:Picolines / Q000737:chemistry
chemical_list: D019428:HIV Integrase Inhibitors; D006877:Hydroxamic Acids; D008024:Ligands; D010847:Picolines; D019427:HIV Integrase; D008274:Magnesium