Synthesis and interaction of 5-(substituted-phenyl)-3-methyl-6,7-dihydropyrazolo[4,3-e] [1,4]diazepin-8(7H)-ones with benzodiazepine receptors in rat cerebral cortex.
On the basis of the anxiolytic property of ripazepam, 1-ethyl-4,6-dihydro-3- methyl-8-phenylpyrazolo[4,3-e][1,4]diazepin-5(1H)-one (1), a series of isomeric 5-(phenyl-substituted)pyrazolo[4,3-e][1,4] diazepin-8-ones 3a-f were prepared and tested for their ability to bind to the benzodiazepine receptor. All compounds 3a-f display affinities for the benzodiazepine receptor in the microM range of concentration; in particular 5-phenyl-3-methyl-6,7-dihydropyrazolo[4,3-e][1,4] diazepin-8(7H)-one (3a) is 2 orders of magnitude less potent in inhibiting [3H]flunitrazepam binding than diazepam and displays an affinity for the benzodiazepine receptor practically comparable to that of its structural isomer, ripazepam, and to that of chloriazepoxide.
Baraldi
P G
PG
Manfredini
S
S
Periotto
V
V
Simoni
D
D
Guarneri
M
M
Borea
P A
PA
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000378:metabolism; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D002707:Chlordiazepoxide / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011720:Pyrazoles / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001381:Azepines; D011720:Pyrazoles; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D002707:Chlordiazepoxide; C009116:ripazepam; D003975:Diazepam