title: Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses.
abstract: 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.
authors.affiliation: Avexa Ltd, 576 Swan Street, Richmond, Victoria 3121, Australia.
authors.forename: Giang
authors.initials: G
authors.lastname: Le
authors.forename: Nick
authors.initials: N
authors.lastname: Vandegraaff
authors.forename: David I
authors.initials: DI
authors.lastname: Rhodes
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jones
authors.forename: Jonathan A V
authors.initials: JA
authors.lastname: Coates
authors.forename: Long
authors.initials: L
authors.lastname: Lu
authors.forename: Xinming
authors.initials: X
authors.lastname: Li
authors.forename: Changjiang
authors.initials: C
authors.lastname: Yu
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.forename: John J
authors.initials: JJ
authors.lastname: Deadman
mesh_terms: 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
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium