Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists

Masakazu Atobe; Kenji Naganuma; Masashi Kawanishi; Akifumi Morimoto; Ken-ichi Kasahara; Shigeki Ohashi; Hiroko Suzuki; Takahiko Hayashi; Shiro Miyoshi

doi:10.1016/j.bmcl.2013.09.032

Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel class of EP1 receptor antagonists

Bioorg Med Chem Lett. 2013 Nov 15;23(22):6064-7. doi: 10.1016/j.bmcl.2013.09.032. Epub 2013 Sep 19.

Authors

Masakazu Atobe¹, Kenji Naganuma, Masashi Kawanishi, Akifumi Morimoto, Ken-ichi Kasahara, Shigeki Ohashi, Hiroko Suzuki, Takahiko Hayashi, Shiro Miyoshi

Affiliation

¹ Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. Electronic address: [email protected].

PMID: 24094816
DOI: 10.1016/j.bmcl.2013.09.032

Abstract

We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol-1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The obtained results suggest that compound 12 provides the best EP1 receptor antagonist activity and demonstrates good oral pharmacokinetics.

Keywords: EP(1) receptor antagonist; HTS; Overactive bladder; Pyrazole; Thiazole.

MeSH terms

Animals
Humans
Mice
Models, Molecular
Pyrazoles / pharmacokinetics
Pyrazoles / pharmacology*
Receptors, Prostaglandin E, EP1 Subtype / antagonists & inhibitors*
Receptors, Prostaglandin E, EP1 Subtype / metabolism
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacokinetics
Thiazoles / pharmacology*

Substances

Pyrazoles
Receptors, Prostaglandin E, EP1 Subtype
Thiazoles