Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted-3'-phenyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel nicotinic antagonist.
A series of 2'-substituted-3'-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3'-position exerted a profound influence on both receptor binding and antinociceptive effects. Substitution of different groups at the 2'-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different.
Carroll
F I
FI
Chemistry and Life Sciences, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
Lee
J R
JR
Navarro
H A
HA
Brieaddy
L E
LE
Abraham
P
P
Damaj
M I
MI
Martin
B R
BR
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018733:Nicotinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D021122:Protein Subunits; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic