Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.

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McMinn DL, Rew Y, Sudom A, Caille S, Degraffenreid M, He X, Hungate R, Jiang B, Jaen J, Julian LD, Kaizerman J, Novak P, Sun D, Tu H, Ursu S, Walker NP, Yan X, Ye Q, Wang Z, Powers JP

Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1446-50. doi: 10.1016/j.bmcl.2009.01.026. Epub 2009 Jan 15.

PubMed ID

19185488 [ View in PubMed

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Abstract

Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-cyclopropyl-N-(trans-4-pyridin-3-ylcyclohexyl)-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamide	Corticosteroid 11-beta-dehydrogenase isozyme 1	IC 50 (nM)	1.7	N/A	N/A	Details