Structure-activity relationship studies of novel pyrazolo[1,5-c][1,3]benzoxazines: synthesis and benzodiazepine...

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.