Trifluoromethyl group as a pharmacophore: Effect of replacing a CF3 group on binding and agonist activity of a glucocorticoid receptor ligand

摘要: Compound 1, a potent glucocorticoid receptor ligand, contains quaternary carbon bearing trifluoromethyl and hydroxyl groups. This paper describes the effect of replacing group on binding agonist activity GR ligand 1. The results illustrate that CF3 with cyclohexylmethyl or benzyl maintains potency. These substitutions alter functional behavior ligands from agonists to antagonists. Docking studies suggest analog 19 binds in similar fashion as antagonist, RU486. central C-11 dimethylaniline moiety RU486 overlay. Binding compound is believed force helix 12 adopt an open conformation this leads antagonist properties non-CF3 carrying large at center molecule.