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

…, LDA Richardson, S Jenkinson, A Spaltenstein…

Index: Miller, John F.; Gudmundsson, Kristjan S.; Richardson, Leah D'Aurora; Jenkinson, Stephen; Spaltenstein, Andrew; Thomson, Michael; Wheelan, Pat Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 10 p. 3026 - 3030

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Citation Number: 18

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.