New indole amide derivatives as potent CRTH2 receptor antagonists

A new series of indole amide acting as hCRTH2 receptor ligands had been explored and are described herein. Several amide derivatives displaying low nanomolar activity in hCRTH2 binding and whole blood assays were identified. They were found to behave as a full antagonists, exhibiting good selectivit...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-06, Vol.21 (11), p.3471-3474
Main Authors: Zaghdane, Helmi, Boyd, Michael, Colucci, John, Simard, Daniel, Berthelette, Carl, Leblanc, Yves, Wang, Zhaoyin, Houle, Robert, Lévesque, Jean François, Molinaro, Carmela, Hamel, Martine, Stocco, Rino, Sawyer, Nicole, Sillaots, Susan, Gervais, François, Gallant, Michel
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Amides - pharmacology
Animals
antagonists
Asthma
Biological and medical sciences
blood
CRTH2 receptor antagonists
DP2 receptor antagonist
Histamine and antagonists. Allergy
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Inhibitory Concentration 50
Ligands
Medical sciences
MK-7246
Molecular Structure
Pharmacology. Drug treatments
Prostaglandin receptors
prostaglandins
Protein Binding - drug effects
Rats
receptors
Receptors, Dopamine D2 - agonists
Respiratory system
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Description
Summary:A new series of indole amide acting as hCRTH2 receptor ligands had been explored and are described herein. Several amide derivatives displaying low nanomolar activity in hCRTH2 binding and whole blood assays were identified. They were found to behave as a full antagonists, exhibiting good selectivity over related prostaglandin receptors. Also, prototypical compounds in this novel series which displayed acceptable CYP profiles and were orally bioavailable in rats were identified.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2011.03.085