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Letters in Drug Design & Discovery

Author(s): O. A. Dasse, J. L. Evans, H.-X. Zhai, D. Zou, J. T. Kintigh, F. Chan, K. Hamilton, E. Hill, J. B. Eckman, P. J. Higgins, A. Volosov, P. Collart, J.-M. Nicolas, R.K. Kondru and C.E. Schwartz

DOI: 10.2174/157018007784619989

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Novel, Acidic CCR2 Receptor Antagonists: Lead Optimization

Page: [263 - 271] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

A unique pyrrolidinone-based CCR2 antagonist with sub-micromolar in vitro activities, good selectivity, and reasonable ADME properties was identified following a screening campaign and subsequent hit-to-lead medicinal chemistry efforts. We now describe further modification of this lead molecule to provide compounds with excellent DMPK profiles and significantly enhanced in vitro activities.

Keywords: MCP-1, CCR2, Chemokine receptor, Antagonist, Medicinal chemistry, Lead optimization, CoMFA, Pharmacophore