The Synthesis of Some Fused Pyrazolo‐1,4‐Naphthoquinones

New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation

“…The physical and analytical data of the compounds are presented in the experimental section along with the IR, 1 H and 13 C spectroscopic data; chemical shifts are reported according to the carbon numbering of compounds 2 in Scheme 3. The common features from the spectral data of compounds 6a-l are closely related to those previously reported for the starting compounds 2a-c [23], and they are as follows:…”

“…The antiproliferative activity of the synthesized compounds was assessed on KATO-III and MCF-7 cell lines using a CellTiter 96 ® AQueous One Solution Proliferation Assay (MTS) from Promega The common features from the spectral data of compounds 6a-l are closely related to those previously reported for the starting compounds 2a-c [23], and they are as follows:…”

“…The new derivatives were prepared using 1H-benzo[f]indazole-4,9-diones 2 (R = -H; -CH2CH2OH; -CH2CH2OAc) as starting substrates, which were conveniently obtained through a direct cyclization reaction of 2-acetyl-6-(4-methylpent-3-enyl)-1,4-naphthoquinone 1 with hydrazines, triethylamine and catalytic glacial acetic acid [23]. The first step of this reaction could be (i) the conjugate addition of the hydrazine to the 1,4-naphthoquinone unit to afford the 3-substituted 1,4-hydroquinone compound 1' or (ii) the condensation reaction between the acetyl group and hydrazine to form the corresponding hydrazone 1T'.…”

“…Starting N-substituted 1H-benzo[f ]indazole-4,9-diones 2a-c were synthesized according to a previously described procedure [23]. IR spectra were recorded on a Perkin Elmer FT IR 1600 spectrophotometer (Norwalk, CN, USA) as a film over NaCl discs.…”

“…In the literature, there are various synthetic methods for preparing 1H-indazoles [8], whereas 1H-indazole-4,7 and 4,9-diones are synthesized via the 1,3-dipolar cycloaddition of diazomethanes to 1,4-quinones [10,[19][20][21][22]. We have recently reported the synthesis of unsubstituted and N-substituted 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f ]indazole-4,9-diones 2 from the reaction of 2-acetyl-6-(4-methylpent-3-enyl)-1,4-naphthoquinone 1 with hydrazine or substituted hydrazines [23]. The objective of this work was to continue previous research on the design and synthesis of new potentially cytotoxic 1,4-naphthoquinone compounds [24,25] while taking into account the enhanced cytotoxic effect that has been observed in drugs or compounds conjugated with amino acids [26,27].…”