Azaindole hydroxamic acids are potent HIV-1 integrase inhibitors.
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.
Plewe
Michael B
MB
Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, California 92121, USA. michael.plewe@pfizer.com
Butler
Scott L
SL
Dress
Klaus R
KR
Hu
Qiyue
Q
Johnson
Ted W
TW
Kuehler
Jon E
JE
Kuki
Atsuo
A
Lam
Hieu
H
Liu
Wen
W
Nowlin
Dawn
D
Peng
Qinghai
Q
Rahavendran
Sadayappan V
SV
Tanis
Steven P
SP
Tran
Khanh T
KT
Wang
Hai
H
Yang
Anle
A
Zhang
Junhu
J
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
D019428:HIV Integrase Inhibitors; D006877:Hydroxamic Acids; D008024:Ligands; D010847:Picolines; D019427:HIV Integrase; D008274:Magnesium