Synthesis and SAR of novel isoquinoline CXCR4 antagonists with potent anti-HIV activity

  • Bioorg Med Chem Lett. 2010 May 15;20(10):3026-30. doi: 10.1016/j.bmcl.2010.03.118.
John F Miller  1 ,  Kristjan S Gudmundsson ,  Leah D'Aurora Richardson ,  Stephen Jenkinson ,  Andrew Spaltenstein ,  Michael Thomson ,  Pat Wheelan
Affiliations
  • 1. Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709-3398, USA. [email protected]
PMID: 20443225 DOI: 10.1016/j.bmcl.2010.03.118
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.