Stereochemical studies on medicinal agents. 19. X-ray crystal structures of two (+/-)-allylprodine diastereomers. The role of the allyl group in conferring high stereoselectivity and potency at analgetic receptors.
X-Ray crystallographic studies have been performed on the two diasteromeric racemates of 3-allyl-1-methyl-4-propionoxypiperidine hydrochloride (allylprodine hydrochloride) in an effort to determine the role of conformation in their interaction with analgetic receptors sites. The chiral orientation of the phenyl group in the highly potent isomer, (+)-1, is qualitatively in conformity with the stereo structure-activity relationship found among other analgetic 4-phenylpiperdines. The fact that (+)-2, a relatively weak analgetic with no stereoselectivity, also possesses this feature indicates that this conformational arrangement per se does not ensure high potency. The data suggest that the very potency and stereoselectivity which the allylic double bond confers to (+)-1 are due primarily to the interaction of this bond with an accessory site on the receptor.
D000498:Allyl Compounds; D000522:Alphaprodine / Q000031:analogs & derivatives*; D000700:Analgesics; D001665:Binding Sites; D003461:Crystallography; D008961:Models, Structural; D008968:Molecular Conformation; D011955:Receptors, Drug; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000498:Allyl Compounds; D000700:Analgesics; D011955:Receptors, Drug; D000522:Alphaprodine