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
  • 1. Roche Palo Alto, Department of Medicinal Chemistry, 3431Hillview Avenue, Palo Alto, CA 94304-1397, USA. [email protected]
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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