title: Identification of novel IP receptor agonists using historical ligand biased chemical arrays.
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.
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. Electronic address: steve.mckeown@novartis.com.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: McKeown
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Charlton
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Cox
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Fitch
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Howson
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Postfach, CH-4002 Basel, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leblanc
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Postfach, CH-4002 Basel, Switzerland.
authors.forename: Arndt
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Rosethorne
authors.affiliation: Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Stanley
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods; D008024:Ligands; D044006:Receptors, Epoprostenol / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D044006:Receptors, Epoprostenol
keywords: IP agonist; PGI(2) agonist; Prostanoid; Pulmonary arterial hypertension