2. Academic Validation
  3. Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981

Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6288-92. doi: 10.1016/j.bmcl.2011.08.124.
Tim Luker 1,  Roger Bonnert,  Steve Brough,  Anthony R Cook,  Mark R Dickinson,  Iain Dougall,  Chris Logan,  Rukhsana T Mohammed,  Stuart Paine,  Hitesh J Sanganee,  Carol Sargent,  Jerzy A Schmidt,  Simon Teague,  Stephen Thom
Affiliations

Affiliation

  • 1 Medicinal Chemistry, AstraZeneca R&D Charnwood, Loughborough, Leicestershire LE11 5RH, UK. tim.luker@astrazeneca.com
PMID: 21944852 DOI: 10.1016/j.bmcl.2011.08.124
Abstract

Novel indole-3-thio-, 3-sulfonyl- and 3-oxy-aryl-1-acetic acids are reported which are potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). Optimization required maintenance of high CRTh2 potency whilst achieving a concomitant reduction in rates of metabolism, removal of cyp p450 inhibition and minimization of Aldose Reductase and aldehyde reductase activity. High quality compounds suitable for in vivo studies are highlighted, culminating in the discovery of AZD1981 (22).

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