A structure-activity analysis of the preferred conformation of the benzyl substituent of tetrahydropapaveroline at the beta receptor.
The effect of restricting the motion of the 3,4-dihydroxybenzyl substituent of tetrahydropapaveroline (THI) on its ability to stimulate the beta adenylate cyclase of the rat erythrocyte was investigated. A number of protoberberines and aporphines were tested as models of two classes of compounds where the benzyl substituent is rigidly but differently fixed. Unexpectedly, the beta agonist activity was associated with both structural types. This could be explained by the assumption that a phenylalanyl or tyrosyl residue of the receptor protein is free to rotate and bind with either position of the benzyl moiety as fixed in the protoberberine and aporphine structures.
D000262:Adenylyl Cyclases / Q000097:blood; D000818:Animals; D001060:Aporphines / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010208:Papaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D001060:Aporphines; D001593:Benzyl Compounds; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D001599:Berberine; D010208:Papaverine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases