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ID: ALA1932948

Journal: Bioorg Med Chem Lett

Title: Discovery of a novel EP2/EP4 dual agonist with high subtype-selectivity.

Authors: Kambe T, Maruyama T, Nakano M, Nakai Y, Yoshida T, Matsunaga N, Oida H, Konaka A, Maruyama T, Nakai H, Toda M.

Abstract: A series of γ-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the ω-chain and aryl moiety in the α-chain were synthesized and biologically evaluated. Among the tested compounds, γ-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2=9.3 nM, mEP4=0.41 nM). A structure-activity relationship study is presented.

CiteXplore: 22119471

DOI: 10.1016/j.bmcl.2011.10.109