Optimization of phenylacetic acid derivatives for balanced CRTH2 and DP dual antagonists

Jiwen Jim Liu; Yingcai Wang; Michael G Johnson; An-Rong Li; Wang Shen; Xuemei Wang; Yongli Su; Matthew Brown; Bettina Van Lengerich; Erika Rickel; Tod Martin; Alison Budelsky; Lisa Seitz; Jay Danao; H Lucy Tang; Tassie Collins; Julio C Medina

doi:10.1016/j.bmcl.2011.12.107

Optimization of phenylacetic acid derivatives for balanced CRTH2 and DP dual antagonists

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1686-9. doi: 10.1016/j.bmcl.2011.12.107. Epub 2011 Dec 30.

Authors

Jiwen Jim Liu¹, Yingcai Wang, Michael G Johnson, An-Rong Li, Wang Shen, Xuemei Wang, Yongli Su, Matthew Brown, Bettina Van Lengerich, Erika Rickel, Tod Martin, Alison Budelsky, Lisa Seitz, Jay Danao, H Lucy Tang, Tassie Collins, Julio C Medina

Affiliation

¹ Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. [email protected]

PMID: 22264478
DOI: 10.1016/j.bmcl.2011.12.107

Abstract

Our first generation CRTH2 and DP dual antagonists, represented by AMG 009, are more potent toward the CRTH2 receptor than to the DP receptor. Here we report our efforts in the discovery of CRTH2 and DP dual antagonists with more balanced potencies to both receptors, such as compound 15.

MeSH terms

Drug Design*
HEK293 Cells
Humans
Inhibitory Concentration 50
Molecular Structure
Phenylacetates / chemical synthesis*
Phenylacetates / chemistry
Phenylacetates / pharmacology
Protein Binding / drug effects
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Prostaglandin / antagonists & inhibitors*

Substances

Phenylacetates
Receptors, Immunologic
Receptors, Prostaglandin
prostanoid D receptor 1, human
phenylacetic acid
prostaglandin D2 receptor