Abstract
Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.
Highlights
Indazole is an important scaffold in medicinal chemistry
A one-pot procedure including a combination of ultrasound synthesis under neat conditions and a Cadogan’s cyclization was implemented for the synthesis of 2-phenyl-2Hindazole derivatives
The biological assays revealed that electron withdrawing groups at the 2-phenyl ring are favorable for antiprotozoal activity
Summary
Indazole is an important scaffold in medicinal chemistry. So far, a few drugs containing the indazole moiety are currently available for clinical use; for instance, the antiemetic granisetron, the nonsteroidal anti-inflammatory drugs benzydamine and bendazac, the anticancer agents pazopanib, axitinib, niraparib and entrectinib. Worldwide 50 million amebiasis cases and 100,000 deaths annually are estimated [10], whereas 280 million people are affected by G. intestinalis [11] Both diseases have high impact in the public health, causing diarrhea, which is a major factor in morbidity and mortality, affecting mainly infant population [12]. 22 indazole derivatives were synthesized employing a practical one-pot process Whereas six of these compounds have been previously reported to have activity against E. histolytica, G. intestinalis, and T. vaginalis, in this study, the activity of the additional 16 compounds against these three parasites was evaluated
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