2. Academic Validation
  3. Azetidinones as vasopressin V1a antagonists

Azetidinones as vasopressin V1a antagonists

  • Bioorg Med Chem. 2007 Mar 1;15(5):2054-80. doi: 10.1016/j.bmc.2006.12.031.
Christophe D Guillon 1,  Gary A Koppel,  Michael J Brownstein,  Michael O Chaney,  Craig F Ferris,  Shi-Fang Lu,  Karine M Fabio,  Marvin J Miller,  Ned D Heindel,  David C Hunden,  Robin D G Cooper,  Stephen W Kaldor,  Jeffrey J Skelton,  Bruce A Dressman,  Michael P Clay,  Mitchell I Steinberg,  Robert F Bruns,  Neal G Simon
Affiliations

Affiliation

  • 1 Department of Chemistry, 6 East Packer Avenue, Lehigh University, Bethlehem, PA 18015, USA. [email protected]
PMID: 17234419 DOI: 10.1016/j.bmc.2006.12.031
Abstract

The azetidinone LY307174 (1) was identified as a screening lead for the vasopressin V1a receptor (IC50 45 nM at the human V1a receptor) based on molecular similarity to ketoconazole (2), a known antagonist of the luteinizing hormone releasing hormone receptor. Structure-activity relationships for the series were explored to optimize receptor affinity and pharmacokinetic properties, resulting in compounds with Ki values <1nM and brain levels after oral dosing approximately 100-fold higher than receptor affinities.

Figures
Products