Synthesis and evaluation of novel pyrazolidinone analogs of PGE2 as EP2 and EP4 receptors agonists.
Replacement of the hydroxy cyclopentanone ring in PGE(2) with chemically more stable heterocyclic rings and substitution of the unsaturated alpha-alkenyl chain with a metabolically more stable phenethyl chain led to the development of potent and selective analogs of PGE(2). Compound 10f showed the highest potency and selectivity for EP(4) the receptor.
Zhao
Zhong
Z
Department of Medicinal Chemistry, EMD-Serono Research Institute, Inc., Rockland, MA 02370, USA. zhong.zhao@genzyme.com
Araldi
Gian Luca
GL
Xiao
Yufang
Y
Reddy
Adulla P
AP
Liao
Yihua
Y
Karra
Srinivasa
S
Brugger
Nadia
N
Fischer
David
D
Palmer
Elizabeth
E
D000818:Animals; D015232:Dinoprostone / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone