Structure-activity relationship studies of novel pyrazolo[1,5-c][1,3]benzoxazines: synthesis and benzodiazepine receptor affinity.
Some 2-arylpyrazolo[1,5-c][1,3]benzoxazin-5-ones 1 and 5- oxopyrazolo[1,5-c][1,3]benzoxazin-2-carboxylates 2 were prepared and biologically evaluated for their binding at benzodiazepine receptor (BZR) in rat cortical membranes. Structure-activity relationship studies suggest that, although proton donor d and proton acceptor a1 are both optional pharmacophoric descriptors, at least one of them must be present for good BZR affinity. When the proton donor d is not present, the heteroatom acceptor a1 is necessary either in the tricyclic core or in the appended substituent at the C-2 to obtain sub-micromolar BZR affinity.
Varano
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Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
Catarzi
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Colotta
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Cecchi
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Filacchioni
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Galli
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Costagli
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010078:Oxazines / Q000138:chemical synthesis* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D010078:Oxazines; D011720:Pyrazoles; D011963:Receptors, GABA-A