Analogues 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 tetranuclear indazolinones. The former were prepared by starting with alkylation of the parent indazolinones (11 or its 5-H analogue). Special mention deserves the method we developed for the direct alkylation of position 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-benzyl-3-methoxyindazoles 14h, i display significant activity. Additional C-13-NMR studies and conformational analysis using molecular mechanics and quantum-mechanical semiempirical techniques confirm that the compounds designed as analogues of the model cytostatic indazolinones are not able to mimic effectively the structural features of the latter.