Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases

  • Bioorg Med Chem Lett. 2011 Jan 1;21(1):288-93. doi: 10.1016/j.bmcl.2010.11.015.
Michel Gallant  1 ,  Christian Beaulieu ,  Carl Berthelette ,  John Colucci ,  Michael A Crackower ,  Chad Dalton ,  Danielle Denis ,  Yves Ducharme ,  Richard W Friesen ,  Daniel Guay ,  François G Gervais ,  Martine Hamel ,  Robert Houle ,  Connie M Krawczyk ,  Birgit Kosjek ,  Stephen Lau ,  Yves Leblanc ,  Ernest E Lee ,  Jean-François Levesque ,  Christophe Mellon ,  Carmela Molinaro ,  Wayne Mullet ,  Gary P O'Neill ,  Paul O'Shea ,  Nicole Sawyer ,  Susan Sillaots ,  Daniel Simard ,  Deborah Slipetz ,  Rino Stocco ,  Dan Sørensen ,  Vouy Linh Truong ,  Elizabeth Wong ,  Jin Wu ,  Helmi Zaghdane ,  Zhaoyin Wang
Affiliations
  • 1. Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada. [email protected]
PMID: 21106375 DOI: 10.1016/j.bmcl.2010.11.015
Abstract

In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.