Discovery of CP-533536: an EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation.
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.
Cameron
Kimberly O
KO
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
Lefker
Bruce A
BA
Ke
Hua Z
HZ
Li
Mei
M
Zawistoski
Michael P
MP
Tjoa
Christina M
CM
Wright
Ann S
AS
DeNinno
Shari L
SL
Paralkar
Vishwas M
VM
Owen
Thomas A
TA
Yu
Li
L
Thompson
David D
DD
D000818:Animals; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C475539:CP533536; C545646:Ptger2 protein, rat; D011725:Pyridines; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013449:Sulfonamides