Synthesis and evaluation of novel pyrazolidinone analogs of PGE(2) as EP2 and EP4 receptors agonists

Department of Medicinal Chemistry, EMD-Serono Research Institute, Inc., Rockland, MA 02370, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.42). 01/2008; 17(23):6572-5. DOI: 10.1016/j.bmcl.2007.09.074
Source: PubMed

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.

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    • "Robust PGE 2 -type analogues have also been prepared through substitution of the native ring system with heterocycles. Thus, γ-lactam (Table 3, entries 6 and 9) (Elworthy et al., 2004; Cameron et al., 2006; Kambe et al., 2012) and pyrazolidinone (Zhao et al., 2007) systems have been used to improve chemical and metabolic stability and to produce analogues with higher EP receptor subtype selectivity. Stable analogues of PGE 3 , the COX-2/PGE synthase-derived product of ω−3 EPA biotransformation, could have value in anticancer drug development. "
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