Discovery of novel and potent CRTH2 antagonists

Shinji Ito; Tadashi Terasaka; Tatsuya Zenkoh; Hiroshi Matsuda; Hisashi Hayashida; Hiroshi Nagata; Yoshimasa Imamura; Miki Kobayashi; Makoto Takeuchi; Mitsuaki Ohta

doi:10.1016/j.bmcl.2011.11.079

Discovery of novel and potent CRTH2 antagonists

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1194-7. doi: 10.1016/j.bmcl.2011.11.079. Epub 2011 Nov 28.

Authors

Shinji Ito¹, Tadashi Terasaka, Tatsuya Zenkoh, Hiroshi Matsuda, Hisashi Hayashida, Hiroshi Nagata, Yoshimasa Imamura, Miki Kobayashi, Makoto Takeuchi, Mitsuaki Ohta

Affiliation

¹ Chemistry Research Labs, Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

PMID: 22178554
DOI: 10.1016/j.bmcl.2011.11.079

Abstract

High throughput screening of our chemical library for CRTH2 antagonists provided a lead compound 1a. Initial optimization of the lead led to the discovery of a novel, potent and orally bioavailable CRTH2 antagonist 17.

MeSH terms

Administration, Oral
Animals
Biological Availability
Dose-Response Relationship, Drug
Drug Discovery*
Guinea Pigs
HEK293 Cells
Humans
Molecular Structure
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Immunologic / metabolism
Receptors, Prostaglandin / antagonists & inhibitors*
Receptors, Prostaglandin / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Receptors, Immunologic
Receptors, Prostaglandin
prostaglandin D2 receptor