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
Letters in Drug Design & Discovery
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:
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.
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Dasse A. O., Evans L. J., Zhai H.-X., Zou D., Kintigh T. J., Chan F., Hamilton K., Hill E., Eckman B. J., Higgins J. P., Volosov A., Collart P., Nicolas J.-M., Kondru R.K. and Schwartz C.E., Novel, Acidic CCR2 Receptor Antagonists: Lead Optimization, Letters in Drug Design & Discovery 2007; 4 (4) . https://dx.doi.org/10.2174/157018007784619989
DOI https://dx.doi.org/10.2174/157018007784619989 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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