Structure activity studies of a series of 4-(m-OH phenyl) piperidines.
A series of 4-(m-OH phenyl)-piperidine analogs with R4 = methyl or t-butyl and NR = methyl, allyl and phenethyl have been synthesized; and their receptor affinities, in vivo analgetic agonism and antagonism, and energy-conformational profiles determined. These analogs bind selectively and with moderate to high affinity to opioid mu-receptors. Binding in their preferred phenyl axial conformation appears to lead to meperidine-like agonism. In addition, for some R4 = methyl but not t-butyl compounds, binding of an energy-accessible phenyl equatorial conformation produces antagonism.
D000700:Analgesics; D008968:Molecular Conformation; D010146:Pain / Q000503:physiopathology; D019800:Phenol; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000700:Analgesics; D010636:Phenols; D010880:Piperidines; D019800:Phenol