Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichagasic drug.

摘要: Abstract Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and benznidazole, is far from satisfactory therefore the development of new antichagasic compounds remains an important goal. On basis properties previously described for some 1,2-disubstituted 5-nitroindazolin-3-ones (21, 33) in order to initiate optimization activity this kind compounds, we have prepared a series related analogs (22–32, 34–38, 58 59) tested in vitro these products against epimastigote forms Trypanosoma cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) 2-benzyl-1-butyl (24) derivatives shown high trypanocidal low unspecific toxicity. Other indazole with different substitution patterns (1-substituted 3-alkoxy-1H-indazoles 2-substituted 3-alkoxy-2H-indazoles), arising synthetic procedures used prepare mentioned indazolinones, moderate effectiveness. The exploration SAR information using concept landscape has been carried out SARANEA software. We also searched structural similarities between 225 known antiprotozoan drugs compound 22. results confirm that 22–24 constitute promising leads 5-nitroindazolin-3-one system novel anti-T. cruzi scaffold which may represent therapeutic alternative treatment disease.