Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists

Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists

A series of trisubstituted cyclohexanes was designed, synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the identification of two distinct substitution patterns about the cyclohexane ring as potent and selective CCR2 antagonists. Compound 36 exhibited excellent bin...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2009-02, Vol.19 (3), p.597-601
Hauptverfasser: Cherney, Robert J., Brogan, John B., Mo, Ruowei, Lo, Yvonne C., Yang, Gengjie, Miller, Persymphonie B., Scherle, Peggy A., Molino, Bruce F., Carter, Percy H., Decicco, Carl P.
Format: Artikel
Sprache:eng
Schlagworte:
Binding Sites
Biological and medical sciences
Calcium - chemistry
CCR2 antagonist
Chemistry, Pharmaceutical - methods
Chemokine CCL2 - chemistry
Chemokines
Chemotaxis
Cyclohexanes - chemistry
Drug Design
Humans
Inhibitory Concentration 50
MCP-1
Medical sciences
Miscellaneous
Models, Chemical
Molecular Structure
Pharmacology. Drug treatments
Protein Binding
Receptors, CCR2 - antagonists & inhibitors
Receptors, CCR2 - chemistry
Structure-Activity Relationship
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Zusammenfassung:A series of trisubstituted cyclohexanes was designed, synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. This led to the identification of two distinct substitution patterns about the cyclohexane ring as potent and selective CCR2 antagonists. Compound 36 exhibited excellent binding (CCR2 IC 50 = 2.4 nM) and functional antagonism (calcium flux IC 50 = 2.0 nM and chemotaxis IC 50 = 5.1 nM).
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2008.12.062