title: 7-Azaindole derivatives as potential partial nicotinic agonists.
abstract: 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.
authors.affiliation: Solvay Pharmaceuticals, Research Laboratories, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. axel.stoit@solvay.com
authors.forename: Axel R
authors.initials: AR
authors.lastname: Stoit
authors.forename: Arnold P
authors.initials: AP
authors.lastname: den Hartog
authors.forename: Harry
authors.initials: H
authors.lastname: Mons
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van Schaik
authors.forename: Nynke
authors.initials: N
authors.lastname: Barkhuijsen
authors.forename: Cees
authors.initials: C
authors.lastname: Stroomer
authors.forename: Hein K A C
authors.initials: HK
authors.lastname: Coolen
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Reinders
authors.forename: Tiny J P
authors.initials: TJ
authors.lastname: Adolfs
authors.forename: Martina
authors.initials: M
authors.lastname: van der Neut
authors.forename: Hiskias
authors.initials: H
authors.lastname: Keizer
authors.forename: Chris G
authors.initials: CG
authors.lastname: Kruse
mesh_terms: 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
chemical_list: 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