1. Azetidinones as vasopressin V1a antagonists
- Author
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Jeffrey J. Skelton, Karine Fabio, Robin D. G. Cooper, Robert F. Bruns, Gary A. Koppel, Stephen W. Kaldor, David C. Hunden, Bruce A. Dressman, Michael P. Clay, Mitchell I. Steinberg, Michael J. Brownstein, Neal G. Simon, Christophe Guillon, Craig F. Ferris, Marvin J. Miller, Michael O. Chaney, Shi-fang Lu, and Ned D. Heindel
- Subjects
Models, Molecular ,Vasopressin ,Magnetic Resonance Spectroscopy ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,CHO Cells ,Spectrometry, Mass, Fast Atom Bombardment ,Pharmacology ,Biochemistry ,Article ,Cricetulus ,Dogs ,Cricetinae ,Drug Discovery ,medicine ,Animals ,Humans ,Receptor ,Molecular Biology ,IC50 ,Chemistry ,Organic Chemistry ,Antagonist ,Brain ,Rats ,Hormone receptor ,Azetidines ,Molecular Medicine ,Ketoconazole ,Luteinizing hormone ,Antidiuretic Hormone Receptor Antagonists ,medicine.drug - 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
- Published
- 2007
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