Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses.
A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were 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
Lu
Long
L
Li
Xinming
X
Yu
Changjiang
C
Feng
Xiao
X
Deadman
John J
JJ
D055808:Drug Discovery; D024882:Drug Resistance, Viral / Q000235:genetics; D006678:HIV / Q000187:drug effects / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D009154:Mutation; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D013329:Structure-Activity Relationship
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium