7-Azaindole derivatives as potential partial nicotinic agonists.
We have investigated a series of 7-azaindoles as potential partial agonists of the alpha4beta2 nicotinic acetylcholine receptor (nAChR). Three series of 7-azaindole derivatives have been synthesized and evaluated for rat brain neuronal nicotinic receptor affinity and functional activity. Compound (+)-51 exhibited the most potent nAChR binding (Ki = 10 nM). Compound 30A demonstrated both moderate binding affinity and partial agonist potency, thus representing a promising lead for the indications of cognition and smoking cessation.
Stoit
Axel R
AR
Solvay Pharmaceuticals, Research Laboratories, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. axel.stoit@solvay.com
den Hartog
Arnold P
AP
Mons
Harry
H
van Schaik
Sjoerd
S
Barkhuijsen
Nynke
N
Stroomer
Cees
C
Coolen
Hein K A C
HK
Reinders
Jan Hendrik
JH
Adolfs
Tiny J P
TJ
van der Neut
Martina
M
Keizer
Hiskias
H
Kruse
Chris G
CG
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001392:Azocines / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D009474:Neurons / Q000378:metabolism; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011807:Quinolizines / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001372:Aza Compounds; D001392:Azocines; D007211:Indoles; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C023422:7-azaindole dimer; C403531:nicotinic receptor alpha4beta2; C004712:cytisine; D000093843:Quinolizidine Alkaloids