| Literature DB >> 17234419 |
Christophe D Guillon1, 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.
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.Entities:
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Year: 2006 PMID： 17234419 PMCID： PMC2067992 DOI： 10.1016/j.bmc.2006.12.031
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641