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 |
- 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
-
Vitamin D and Infectious Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Microfluidic Paper-based Device for Medicinal Diagnosis
Current Topics in Medicinal Chemistry Herpes Simplex Virus Type 1 Amplicons and their Hybrid Virus Partners, EBV, AAV, and Retrovirus
Current Gene Therapy The ERK 1 and 2 Pathway in the Nervous System: From Basic Aspects to Possible Clinical Applications in Pain and Visceral Dysfunction
Current Neuropharmacology Albumin Induces Neuroprotection Against Ischemic Stroke by Altering Toll-Like Receptor 4 and Regulatory T Cells in Mice
CNS & Neurological Disorders - Drug Targets Leukocyte Influx in Atherosclerosis
Current Drug Targets The Clinical Utility of Kidney Injury Molecule 1 in the Prediction, Diagnosis and Prognosis of Acute Kidney Injury: A Systematic Review
Inflammation & Allergy - Drug Targets (Discontinued) Cyclosporin and Organ Specific Toxicity: Clinical Aspects, Pharmacogenetics and Perspectives
Current Clinical Pharmacology Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy
Current Clinical Pharmacology A Snapshot of Tissue Glycerolipids
Current Pharmaceutical Design Baculovirus as Vaccine Vectors
Current Gene Therapy Nebulizer Therapy in Pulmonology: Review of the Literature
Current Respiratory Medicine Reviews Drug Loaded Erythrocytes: As Novel Drug Delivery System
Current Pharmaceutical Design In vitro Effects of Polyphenols on the Peripheral Immune Responses in Nickel-sensitized Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial
Recent Patents on Inflammation & Allergy Drug Discovery Paracrine Mechanisms Involved in Mesenchymal Stem Cell Differentiation into Cardiomyocytes
Current Stem Cell Research & Therapy Phosphate-Affinity Gel Electrophoresis Using a Phos-Tag Molecule for Phosphoproteome Study
Current Proteomics Patterns of Self-Medication with Medicinal Plants and Related Adverse Events - A South American Survey
Current Drug Safety Immunological Mechanisms of Specific Allergen Immunotherapy
Inflammation & Allergy - Drug Targets (Discontinued) Cilostazol in the Management of Atherosclerosis
Current Vascular Pharmacology