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ID: ALA1137967

Journal: Bioorg Med Chem Lett

Title: Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization.

Authors: Elworthy TR, Kertesz DJ, Kim W, Roepel MG, Quattrocchio-Setti L, Smith DB, Tracy JL, Chow A, Li F, Brill ER, Lach LK, McGee D, Yang DS, Chiou SS.

Abstract: A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP(4) receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP(4) versus the other EP prostanoid receptors.

CiteXplore: 15026044

DOI: 10.1016/j.bmcl.2004.01.063