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

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

  • Bioorg Med Chem Lett. 2004 Apr 5;14(7):1655-9. doi: 10.1016/j.bmcl.2004.01.063.
Todd R Elworthy 1,  Denis J Kertesz,  Woongki Kim,  Michael G Roepel,  Lina Quattrocchio-Setti,  David B Smith,  Jahari Laurant Tracy,  Audrey Chow,  Fujun Li,  Emma R Brill,  Leang K Lach,  Daren McGee,  Diana S Yang,  San-San Chiou
Affiliations

Affiliation

  • 1 Roche Palo Alto, Department of Medicinal Chemistry, 3431Hillview Avenue, Palo Alto, CA 94304-1397, USA. todd.elworthy@roche.com
PMID: 15026044 DOI: 10.1016/j.bmcl.2004.01.063
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.

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