New indole amide derivatives as potent CRTH2 receptor antagonists

Helmi Zaghdane; Michael Boyd; John Colucci; Daniel Simard; Carl Berthelette; Yves Leblanc; Zhaoyin Wang; Robert Houle; Jean François Lévesque; Carmela Molinaro; Martine Hamel; Rino Stocco; Nicole Sawyer; Susan Sillaots; François Gervais; Michel Gallant

doi:10.1016/j.bmcl.2011.03.085

New indole amide derivatives as potent CRTH2 receptor antagonists

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3471-4. doi: 10.1016/j.bmcl.2011.03.085. Epub 2011 Mar 30.

Authors

Helmi Zaghdane¹, Michael Boyd, John Colucci, Daniel Simard, Carl Berthelette, Yves Leblanc, Zhaoyin Wang, Robert Houle, Jean François Lévesque, Carmela Molinaro, Martine Hamel, Rino Stocco, Nicole Sawyer, Susan Sillaots, François Gervais, Michel Gallant

Affiliation

¹ Medicinal Chemistry, Merck Frosst, Center of Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Quebec, Canada H9H 3L1. Zaghdane.helmi@courrier.uqam.ca

PMID: 21515053
DOI: 10.1016/j.bmcl.2011.03.085

Abstract

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.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology*
Animals
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Inhibitory Concentration 50
Ligands
Molecular Structure
Protein Binding / drug effects
Rats
Receptors, Dopamine D2 / agonists*

Substances

Amides
Indoles
Ligands
Receptors, Dopamine D2