title: High affinity central benzodiazepine receptor ligands: synthesis and structure-activity relationship studies of a new series of pyrazolo[4,3-c]quinolin-3-ones.
abstract: A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin- 3-(3H)-ones, carrying appropriate substituents at the quinoline and N2-phenyl rings, were prepared and tested as central benzodiazepine receptor ligands. Results from structure-affinity relationship studies were in full agreement with previously proposed pharmacophore models and, in addition, quantitative structure-activity analysis gave further significant insight into the main molecular determinants of high benzodiazepine receptor affinity. The intrinsic activity of some active ligands was also determined and preliminary discussed.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi, Siena, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Savini
authors.forename: P
authors.initials: P
authors.lastname: Massarelli
authors.forename: C
authors.initials: C
authors.lastname: Nencini
authors.forename: C
authors.initials: C
authors.lastname: Pellerano
authors.forename: G
authors.initials: G
authors.lastname: Biggio
authors.forename: A
authors.initials: A
authors.lastname: Maciocco
authors.forename: G
authors.initials: G
authors.lastname: Tuligi
authors.forename: A
authors.initials: A
authors.lastname: Carrieri
authors.forename: N
authors.initials: N
authors.lastname: Cinone
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D046508:Culture Techniques; D005445:Flunitrazepam / Q000378:metabolism; D018755:GABA Agonists / Q000737:chemistry* / Q000378:metabolism; D018756:GABA Antagonists / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D008024:Ligands; D011720:Pyrazoles; D015363:Quinolones; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one