Design, Synthesis and Biological Evaluation of Novel Indazole Compounds with Potential Therapeutic Activity

Abstract

Heterocycle scaffold, especially nitrogen-containing heterocycle such as indole, indazole, and imidazole, are important building blocks for some bioactive natural products and preclinical/clinical drugs, which have attracted more and more attention from overall world chemical scientists. As one of the most crucial nitrogen-containing heterocycle families, indazole and its structurally diverse derivatives have played a vital role because of their chemical and biological properties. Emil Fisher defined indazole as a pyrazole ring fused with the benzene ring, which is also called benzpyrazole or isoindazole heterocyclic molecules. The planarity of the indazole ring, various side chain substitutions of different lengths and positional functionalization can lead to a variety of derivatives that had attracted much attention in the past, as well as in recent years, because of their different kinds of biological properties, such as anti-inflammatory, antibacterial, anti-HIV, and antitumor. To date, it needs to be pointed out at least 43 indazole-based therapeutic agents have been in the clinical application or clinical trials. Herein, we attempted to describe the development and biological property of indazole-based agents. We hope our work will provide useful clues for the discovery and rational design of indazole-containing derivatives as potent drug candidates. The current work is organized into three major parts, each of which deals with a separate topic underlying alternative design approaches and synthesizing distinct indazoles, as well as studying their biological activity against various targets. The present thesis can be subdivided into the following chapters: