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 e valuated for their binding at benzodiazepine receptor (BZR) in rat cor tical membranes. Structure-activity relationship studies suggest that, although proton donor d and proton acceptor a(1) are both optional ph armacophoric descriptors, at least one of them must be present for goo d BZR affinity. When the proton donor d is not present, the heteroatom acceptor a(1) is necessary either in the tricyclic core or in the app ended substituent at the C-2 to obtain sub-micromolar BZR affinity.