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.
Export Options
About this article
Cite this article as:
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 |
Related Journals
Related Books
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Uridine Function in the Central Nervous System
Current Topics in Medicinal Chemistry Interaction of Probenecid with the Breast Cancer Resistance Protein Transporter (BCRP/ABCG2)
Letters in Drug Design & Discovery Commercially Available, FDA-approved Epigenetic Modifiers As Therapeutic Agents in Bacterial Infection
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) Toll-like Receptor as a Molecular Link between Metabolic Syndrome and Inflammation: A Review
Current Drug Targets Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to Therapeutic Perspectives
Central Nervous System Agents in Medicinal Chemistry Tendon Regeneration and Repair with Adipose Derived Stem Cells
Current Stem Cell Research & Therapy Understanding the Immune and Inflammatory Response to Rhinoviruses: Recent Advances with Relevance to Asthma
Current Respiratory Medicine Reviews Plasticity in Uterine Innervation: State of the Art
Current Protein & Peptide Science Effect of Botanicals on Inflammation and Skin Aging: Analyzing the Evidence
Inflammation & Allergy - Drug Targets (Discontinued) On the Cellular and Molecular Regulatory Transcriptional Mechanisms and Responsive Putative Pathways to Inflammatory Oxidative Stress Revisited: Current Immunological Breakthroughs and Views at a Glance
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Genetic Vaccination for the Immunotherapy of B-Cell Malignancies
Current Gene Therapy A Review of Herbal Remedies for Multiple Sclerosis-Like Disorders in Traditional Persian Medicine (TPM)
Current Drug Metabolism Recent Progress on Tumor Missile Therapy and Tumor Vascular Targeting Therapy as a New Approach
Current Vascular Pharmacology Amyloid β -Protein Assembly as a Therapeutic Target of Alzheimers Disease
Current Pharmaceutical Design Metabolic Syndrome and Adipose Tissue: New Clinical Aspects and Therapeutic Targets
Current Pharmaceutical Design A Role for SHIP in Stem Cell Biology and Transplantation
Current Stem Cell Research & Therapy Rexinoids for Prevention and Treatment of Cancer: Opportunities and Challenges
Current Topics in Medicinal Chemistry Biological Treatments for SAPHO Syndrome: An Update
Inflammation & Allergy - Drug Targets (Discontinued) Fluorescent GPCR Ligands as New Tools in Pharmacology-Update, Years 2008- Early 2014
Current Medicinal Chemistry Fenofibrate: A New Treatment for Diabetic Retinopathy. Molecular Mechanisms and Future Perspectives
Current Medicinal Chemistry