title: Synthesis and SAR of novel isoquinoline CXCR4 antagonists with potent  anti-HIV activity.
abstract: Using AMD070 as a starting point for structural modification, a novel series of isoquinoline CXCR4 antagonists was developed. A structure-activity scan of alternate lower heterocycles led to the 3-isoquinolinyl moiety as an attractive replacement for benzimidazole. Side chain optimization in the isoquinoline series led to a number of compounds with low nanomolar anti-HIV activities and promising rat PK properties.
authors.affiliation: Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709-3398, USA. john.6.miller@gsk.com
authors.forename: John F
authors.initials: JF
authors.lastname: Miller
authors.forename: Kristjan S
authors.initials: KS
authors.lastname: Gudmundsson
authors.forename: Leah
authors.initials: L
authors.lastname: D'Aurora Richardson
authors.forename: Stephen
authors.initials: S
authors.lastname: Jenkinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Spaltenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Thomson
authors.forename: Pat
authors.initials: P
authors.lastname: Wheelan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001562:Benzimidazoles; D007546:Isoquinolines; D019718:Receptors, CXCR4; C031000:benzimidazole