Literature DB >> 19036582

Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain.

Adrian Hall1, Susan H Brown, Christopher Budd, Nicholas M Clayton, Gerard M P Giblin, Paul Goldsmith, Thomas G Hayhow, David N Hurst, Alan Naylor, D Anthony Rawlings, Tiziana Scoccitti, Alexander W Wilson, Wendy J Winchester.   

Abstract

Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP(1) receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 414.9g/mol and poor in vivo metabolic stability in the rat and resulted in the identification of compound 7i (GSK345931A) which demonstrated good metabolic stability in the rat and lower molecular weight (381.9g/mol). In addition, 7i (GSK345931A) showed measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain.

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Year:  2008        PMID： 19036582     DOI： 10.1016/j.bmcl.2008.11.032

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  9 in total

1.  Concise Synthesis of Functionalized Benzocyclobutenones.

Authors:  Peng-Hao Chen; Nikolas A Savage; Guangbin Dong
Journal:  Tetrahedron       Date:  2014-07-08       Impact factor: 2.457

2.  Inhibition of the Prostaglandin EP-1 Receptor in Periosteum Progenitor Cells Enhances Osteoblast Differentiation and Fracture Repair.

Authors:  Marina Feigenson; Jennifer H Jonason; Jie Shen; Alayna E Loiselle; Hani A Awad; Regis J O'Keefe
Journal:  Ann Biomed Eng       Date:  2019-04-12       Impact factor: 3.934

Review 3.  Novel strategies for the treatment of inflammatory hyperalgesia.

Authors:  Atul R Chopade; Wahid A Mulla
Journal:  Eur J Clin Pharmacol       Date:  2010-02-13       Impact factor: 2.953

4.  A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced heartburn symptoms in healthy male volunteers: a randomized clinical trial.

Authors:  Takashi Kondo; Hiroo Sei; Takahisa Yamasaki; Toshihiko Tomita; Yoshio Ohda; Tadayuki Oshima; Hirokazu Fukui; Jiro Watari; Hiroto Miwa
Journal:  J Gastroenterol       Date:  2017-01-24       Impact factor: 7.527

5.  Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A.

Authors:  Thor Ostenfeld; Claire Beaumont; Jonathan Bullman; Maria Beaumont; Phillip Jeffrey
Journal:  Br J Clin Pharmacol       Date:  2012-12       Impact factor: 4.335

6.  Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere.

Authors:  Jason D Downey; Sam A Saleh; Thomas M Bridges; Ryan D Morrison; J Scott Daniels; Craig W Lindsley; Richard M Breyer
Journal:  Bioorg Med Chem Lett       Date:  2012-11-24       Impact factor: 2.823

7.  The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the prostaglandin E2 human model of headache.

Authors:  Maria Antonova; Troels Wienecke; Karen Maubach; Emma Thomas; Jes Olesen; Messoud Ashina
Journal:  J Headache Pain       Date:  2011-06-17       Impact factor: 7.277

8.  Quantitative analysis of lipids: a higher-throughput LC-MS/MS-based method and its comparison to ELISA.

Authors:  Adarsh S Gandhi; David Budac; Tanzilya Khayrullina; Roland Staal; Gamini Chandrasena
Journal:  Future Sci OA       Date:  2017-01-16

9.  Prostaglandin E2 Induces Skin Aging via E-Prostanoid 1 in Normal Human Dermal Fibroblasts.

Authors:  Joong Hyun Shim
Journal:  Int J Mol Sci       Date:  2019-11-07       Impact factor: 5.923
  9 in total

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