Synthesis and pharmacological characterization of exo-2-(2'-chloro-5-pyridinyl)-7-(endo and exo)-aminobicyclo[2.2.1]heptanes as novel epibatidine analogues.
Procedures were developed for the synthesis of exo-(2'-chloro-5-pyridinyl)-7-(endo and exo)-amino[2.2.1]heptanes (3a and 3b). The compounds were evaluated for binding to the alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs), for pharmacological activity in the mouse tail-flick and hot-plate assays, and for hypothermia and locomotor activity. Compounds 3a and 3b possessed alpha4beta2 nAChR binding properties similar to those of (-)-nicotine and were nAChR agonists in all four mouse assays.
Carroll
F Ivy
FI
Chemistry and Life Sciences, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
Brieaddy
Lawrence E
LE
Navarro
Hernán A
HA
Damaj
M I
MI
Martin
Billy R
BR
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009636:Norbornanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D008024:Ligands; D018722:Nicotinic Agonists; D009636:Norbornanes; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine; C082748:epibatidine