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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
Author(s) -
Arán Vicente J.,
Flores María,
Muñoz Pilar,
Páez Juan A.,
SánchezVerdú Prado,
Stud Manfred
Publication year - 1996
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199619960507
Subject(s) - hela , chemistry , alkylation , halide , stereochemistry , combinatorial chemistry , proton nmr , organic chemistry , in vitro , biochemistry , catalysis
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 13 C‐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.