Preparation of cycloalkylpyrazole derivatives for use as FXR modulators.

Abstract

Title compds. I [A = CH2 or (CH2)3; R1 = (un)substituted Ph, naphthyl or heteroaryl; R2 = H, Me, Et, OH, OMe, F, CH2F, CHF2, or CF3; R3 = heterocyclyl, cycloalkylalkyl, (un)substituted cycloalkyl, or Ph; R4 = C(O)NH(alkyl), CH2O-alkyl, (un)substituted OPh, etc.], and their pharmaceutically acceptable salts, are prepd. and disclosed as FXR modulators. Thus, e.g., II was prepd. by multistep procedure (prepn. given). I were evaluated in FXR radioligand binding assays, e.g., II demonstrated an IC50 value of 28.7 μM. [on SciFinder(R)]