Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.

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Crombie AL, Antrilli TM, Campbell BA, Crandall DL, Failli AA, He Y, Kern JC, Moore WJ, Nogle LM, Trybulski EJ

Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists.

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3742-5. doi: 10.1016/j.bmcl.2010.04.068. Epub 2010 Apr 21.

PubMed ID
20471258 [ View in PubMed
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Abstract

A series of biaryl amides containing an azabicyclooctane amine headpiece were synthesized and evaluated as mixed arginine vasopressin (AVP) receptor antagonists. Several analogues, including 8g, 12g, 13d, and 13g, were shown to have excellent V(1a)- and good V(2)-receptor binding affinities. Compound 13d was further profiled for drug-like properties and for an in vitro comparison with conivaptan, the program's mixed V(1a)/V(2)-receptor antagonist standard.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ConivaptanVasopressin V1a receptorKi (nM)0.43N/AN/ADetails
ConivaptanVasopressin V1a receptorIC 50 (nM)3N/AN/ADetails
ConivaptanVasopressin V2 receptorKi (nM)0.36N/AN/ADetails
ConivaptanVasopressin V2 receptorIC 50 (nM)11N/AN/ADetails