ANALOGS OF CYTOSTATIC, FUSED INDAZOLINONES - SYNTHESIS, CONFORMATIONAL-ANALYSIS AND CYTOSTATIC ACTIVITY AGAINST HELA-CELLS OF SOME 1-SUBSTITUTED INDAZOLOLS, 2-SUBSTITUTED INDAZOLINONES, AND RELATED-COMPOUNDS

A number of indazol-3-ol and indazolin-3-one derivatives were designed as open-chain analogues of some previously studied cytostatic tetranu clear indazolinones. The former were prepared by starting with alkylat ion of the parent indazolinones (11 or its 5-H analogue). Special ment ion deserves the method we developed for the direct alkylation of posi tion 2 of indazolinone 11 with benzyl or picolyl halides. The prepared compounds were evaluated as cytostatic agents against HeLa cells, but only 1-benzylindazolol 5a and 1-(2-fluorobenzyl)-3-methoxy- and 1-ben zyl-3-methoxyindazoles 14h, i display significant activity. Additional C-13-NMR studies and conformational analysis using molecular mechanic s and quantum-mechanical semiempirical techniques confirm that the com pounds designed as analogues of the model cytostatic indazolinones are not able to mimic effectively the structural features of the latter.