Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: azoles: effective metal chelators.
Synthesis of a diverse set of azoles and their utilizations as an amide isostere in the design of HIV integrase inhibitors is described. The Letter identified thiazole, oxazole, and imidazole as the most promising heterocycles. Initial SAR studies indicated that these novel series of integrase inhibitors are amenable to lead optimization. Several compounds with low nanomolar inhibitory potency are reported.
Le
Giang
G
Avexa Ltd, 576 Swan Street, Richmond, Victoria 3121, Australia.
Vandegraaff
Nick
N
Rhodes
David I
DI
Jones
Eric D
ED
Coates
Jonathan A V
JA
Thienthong
Neeranat
N
Winfield
Lisa J
LJ
Lu
Long
L
Li
Xinming
X
Yu
Changjiang
C
Feng
Xiao
X
Deadman
John J
JJ
D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008670:Metals / Q000737:chemistry*; D013329:Structure-Activity Relationship
D001393:Azoles; D001643:Bridged Bicyclo Compounds; D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D008670:Metals; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1