Identification of novel IP receptor agonists using historical ligand biased chemical arrays

Stephen C McKeown; Steven J Charlton; Brian Cox; Helen Fitch; Christopher D Howson; Catherine Leblanc; Arndt Meyer; Elizabeth M Rosethorne; Emily Stanley

doi:10.1016/j.bmcl.2014.03.089

Identification of novel IP receptor agonists using historical ligand biased chemical arrays

Bioorg Med Chem Lett. 2014 May 15;24(10):2247-50. doi: 10.1016/j.bmcl.2014.03.089. Epub 2014 Apr 5.

Authors

Stephen C McKeown¹, Steven J Charlton², Brian Cox², Helen Fitch², Christopher D Howson², Catherine Leblanc³, Arndt Meyer³, Elizabeth M Rosethorne², Emily Stanley²

Affiliations

¹ Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. Electronic address: [email protected].
² Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
³ Novartis Pharma AG, Novartis Institutes for BioMedical Research, Postfach, CH-4002 Basel, Switzerland.

PMID: 24736116
DOI: 10.1016/j.bmcl.2014.03.089

Abstract

By considering published structural information we have designed high throughput biaryl lipophilic acid arrays leveraging facile chemistry to expedite their synthesis. We rapidly identified multiple hits which were of suitable IP agonist potency. These relatively simple and strategically undecorated molecules present an ideal opportunity for optimization towards our target candidate profile.

Keywords: IP agonist; PGI(2) agonist; Prostanoid; Pulmonary arterial hypertension.

MeSH terms

Antihypertensive Agents / chemistry*
Antihypertensive Agents / pharmacology*
Bridged Bicyclo Compounds / chemistry*
Bridged Bicyclo Compounds / pharmacology*
High-Throughput Screening Assays / methods
Ligands
Receptors, Epoprostenol / agonists*
Receptors, Epoprostenol / chemistry
Structure-Activity Relationship

Substances

Antihypertensive Agents
Bridged Bicyclo Compounds
Ligands
Receptors, Epoprostenol