Title: Novel, Acidic CCR2 Receptor Antagonists: Lead Optimization
VOLUME: 4 ISSUE: 4
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
Affiliation:Resolvyx Pharmaceuticals,Bedford, MA, USA.
Keywords:MCP-1, CCR2, Chemokine receptor, Antagonist, Medicinal chemistry, Lead optimization, CoMFA, Pharmacophore
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.
