Synthesis and biological characterization of pyridohomotropanes. Structure-activity relationships of conformationally restricted nicotinoids.
The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity comparable to that of the highly potent agonist, anatoxin a. The inactivity observed relative to PHT of N-methyl- and 2'-methyl-PHT has helped to further define the structure-activity requirements of conformationally restricted nicotinoids.
Kanne
D B
DB
Stauffer Chemical Company, Richmond, California.
Abood
L G
LG
D000818:Animals; D001921:Brain / Q000187:drug effects; D002217:Carbachol / Q000031:analogs & derivatives / Q000378:metabolism; D004557:Electric Organ / Q000187:drug effects; D005731:Ganglionic Stimulants / Q000138:chemical synthesis* / Q000378:metabolism; D066298:In Vitro Techniques; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D013329:Structure-Activity Relationship; D014101:Torpedo; D014326:Tropanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D005731:Ganglionic Stimulants; D011725:Pyridines; D011978:Receptors, Nicotinic; D014326:Tropanes; C055134:pyrido(3,4-b)norhomotropane; C053765:N-methylcarbamylcholine; D009538:Nicotine; C005311:nornicotine; D002217:Carbachol