Synthesis and evaluation of novel pyrazolidinone analogs of PGE2 as EP2 and EP4 receptors agonists

Zhong Zhao; Gian Luca Araldi; Yufang Xiao; Adulla P Reddy; Yihua Liao; Srinivasa Karra; Nadia Brugger; David Fischer; Elizabeth Palmer

doi:10.1016/j.bmcl.2007.09.074

Synthesis and evaluation of novel pyrazolidinone analogs of PGE2 as EP2 and EP4 receptors agonists

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6572-5. doi: 10.1016/j.bmcl.2007.09.074. Epub 2007 Sep 26.

Authors

Zhong Zhao¹, Gian Luca Araldi, Yufang Xiao, Adulla P Reddy, Yihua Liao, Srinivasa Karra, Nadia Brugger, David Fischer, Elizabeth Palmer

Affiliation

¹ Department of Medicinal Chemistry, EMD-Serono Research Institute, Inc., Rockland, MA 02370, USA. zhong.zhao@genzyme.com

PMID: 17931866
DOI: 10.1016/j.bmcl.2007.09.074

Abstract

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.

Publication types

Comparative Study

MeSH terms

Animals
Dinoprostone / chemical synthesis*
Dinoprostone / pharmacology
Drug Evaluation, Preclinical
Female
Humans
Mice
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology
Rats
Receptors, Prostaglandin E / agonists*
Receptors, Prostaglandin E / physiology
Receptors, Prostaglandin E, EP2 Subtype
Receptors, Prostaglandin E, EP4 Subtype

Substances

PTGER2 protein, human
PTGER4 protein, human
Ptger2 protein, mouse
Ptger4 protein, mouse
Pyrazoles
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP2 Subtype
Receptors, Prostaglandin E, EP4 Subtype
Dinoprostone