Structure-activity relationships within a series of analogues of the histamine H1-antagonist terfenadine

Article abstract of DOI:10.1016/0223-5234(93)90009-4

A number of terfenadine derivatives including terfenadine enantiomers were synthesized and tested for histamine H₁-receptor affinity. No significant differences in H₁ activity were found between terfenadine enantiomers. Qualitative structure-activity relationship studies identified the α,α-diphenyl-4-piperidinomethanol moiety as the pharmacophore for the H₁ activity of this group of compounds. The major role of the phenylbutanol moiety in terfenadine seems to be preventing the compound from crossing the blood-brain barrier.