Discovery of a new series of potent prostacyclin receptor agonists with in vivo activity in rat

Thuy-Anh Tran; Young-Jun Shin; Bryan Kramer; Juyi Choi; Ning Zou; Pureza Vallar; Peter Martens; P Douglas Boatman; John W Adams; Juan Ramirez; Yunqing Shi; Michael Morgan; David J Unett; Steve Chang; Hsin-Hui Shu; Shiu-Feng Tung; Graeme Semple

doi:10.1016/j.bmcl.2015.01.024

Discovery of a new series of potent prostacyclin receptor agonists with in vivo activity in rat

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1030-5. doi: 10.1016/j.bmcl.2015.01.024. Epub 2015 Jan 22.

Authors

Thuy-Anh Tran¹, Young-Jun Shin¹, Bryan Kramer¹, Juyi Choi¹, Ning Zou¹, Pureza Vallar¹, Peter Martens¹, P Douglas Boatman¹, John W Adams¹, Juan Ramirez¹, Yunqing Shi¹, Michael Morgan¹, David J Unett¹, Steve Chang¹, Hsin-Hui Shu¹, Shiu-Feng Tung¹, Graeme Semple²

Affiliations

¹ Arena Pharmaceuticals, 6154, Nancy Ridge Drive, San Diego, CA 92121, USA.
² Arena Pharmaceuticals, 6154, Nancy Ridge Drive, San Diego, CA 92121, USA. Electronic address: gsemple@arenapharm.com.

PMID: 25666818
DOI: 10.1016/j.bmcl.2015.01.024

Abstract

The design and synthesis of two closely related series of prostacyclin receptor agonist compounds that showed excellent human IP receptor potency and efficacy is described. Compounds from this series showed in vivo activity after SC dosing in the monocrotaline model of PAH in rat.

Keywords: GPCR; IP receptor agonist; PAH; Prostacyclin.

MeSH terms

Animals
Drug Discovery*
Humans
Hypertension, Pulmonary / chemically induced
Hypertension, Pulmonary / drug therapy*
Monocrotaline
Platelet Aggregation / drug effects
Rats
Receptors, Prostaglandin / agonists*
Receptors, Prostaglandin / metabolism

Substances

Receptors, Prostaglandin
Monocrotaline