Discovery of CP-533536: an EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation

Kimberly O Cameron; Bruce A Lefker; Hua Z Ke; Mei Li; Michael P Zawistoski; Christina M Tjoa; Ann S Wright; Shari L DeNinno; Vishwas M Paralkar; Thomas A Owen; Li Yu; David D Thompson

doi:10.1016/j.bmcl.2009.01.059

Discovery of CP-533536: an EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation

Bioorg Med Chem Lett. 2009 Apr 1;19(7):2075-8. doi: 10.1016/j.bmcl.2009.01.059. Epub 2009 Jan 23.

Authors

Kimberly O Cameron¹, Bruce A Lefker, Hua Z Ke, Mei Li, Michael P Zawistoski, Christina M Tjoa, Ann S Wright, Shari L DeNinno, Vishwas M Paralkar, Thomas A Owen, Li Yu, David D Thompson

Affiliation

¹ Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. kimberly.o.cameron@pfizer.com

PMID: 19250823
DOI: 10.1016/j.bmcl.2009.01.059

Abstract

Sulfonamides, exemplified by 3a, were identified as highly selective EP(2) agonists. Lead optimization led to the identification of CP-533536, 7f, a potent and selective EP(2) agonist. CP-533536 demonstrated the ability to heal fractures when administered locally as a single dose in rat models of fracture healing.

MeSH terms

Animals
Male
Osteogenesis / drug effects*
Pyridines / administration & dosage
Pyridines / chemistry*
Pyridines / pharmacokinetics
Rats
Rats, Sprague-Dawley
Receptors, Prostaglandin E / agonists*
Receptors, Prostaglandin E / metabolism
Receptors, Prostaglandin E, EP2 Subtype
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

CP533536
Ptger2 protein, rat
Pyridines
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP2 Subtype
Sulfonamides