High affinity central benzodiazepine receptor ligands: synthesis and structure-activity relationship studies of a new series of pyrazolo[4,3-c]quinolin-3-ones.
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.
Savini
L
L
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi, Siena, Italy.
Massarelli
P
P
Nencini
C
C
Pellerano
C
C
Biggio
G
G
Maciocco
A
A
Tuligi
G
G
Carrieri
A
A
Cinone
N
N
Carotti
A
A
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
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