Conformations and "nictinic" activites of cyclic analogues of choline aryl ether.
The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the minimum torsional angles about the aryl-oxygen gond geing 20, 20, 80, and 27 degrees, respectively. Since the piperidinium compound stimulates ganglia, it is concluded the either planarity of the aryl--O--C system is not essential for this type of activity or receptor interaction can involve appreciable bond distortion. The absence of ganglion-stimulant activity in the remaining compounds indicates the need for a transoid arrangement of the O--C--C--N+ system.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D005731:Ganglionic Stimulants / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005731:Ganglionic Stimulants; D010647:Phenyl Ethers; D002794:Choline