Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions.

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00°/m in, typical half-height peak width = 0.15° 3.0

Several substituted 2- and 4-hydroxyacetophenones are linked to Wang resin via a modified Mitsunobu protocol. These resin-bound acetophenones are condensed with aromatic aldehydes, and the resulting chalcones 5 are used for the synthesis of 2-dialkylamino- (9a-d) and 2-alkylamino-4,6-diarylpyridines (11a-f), and 2-alkyl-4,6-diaryl- (14a) and 2,4,6-triarylpyrimidines (14b,c) in a manner suitable for combinatorial applications.

The condensation of α,β‐unsaturated ketones with substituted o‐aminothiophenols, obtained by reductive cleavage of the corresponding disulfides in the presence of triphenylphosphine, is an effective method for the synthesis of 2,4‐diaryl‐2,3‐dihydro‐1,5‐benzothiazepines under neutral conditions.