Recent Advances in the Development of Indazole‐based Anticancer Agents

Abstract

Cancer is one of the leading causes of human mortality globally; therefore, intensive efforts have been made to seek new active drugs with improved anticancer efficacy. Indazole-containing derivatives are endowed with a broad range of biological properties, including anti-inflammatory, antimicrobial, anti-HIV, antihypertensive, and anticancer activities. In recent years, the development of anticancer drugs has given rise to a wide range of indazole derivatives, some of which exhibit outstanding activity against various tumor types. The aim of this review is to outline recent developments concerning the anticancer activity of indazole derivatives, as well as to summarize the design strategies and structure-activity relationships of these compounds.

Transition‐Metal‐Catalyzed Syntheses of Indazoles

“…Indazoles, the bioisosteres of indoles, are excellent pharmacophores having a wide range of biological and pharmaceutical applications. [3,4] Many commercially available drugs contain this potent scaffold. Their biological properties include anti-inflammatory, antimicrobial, antihypertensive, and antiallergic activities.…”

“…Structurally diverse indazole derivatives contributed significantly to the progress of pharmacology over the decades. [1,3,4,5] The importance of indazole in both -biomedical and material chemistry -together with their scarce occurrence in nature, inspired the researchers to develop novel methods for the synthesis of indazoles. Early approaches towards the synthesis of indazoles were largely based on metal-free classical synthetic routes such as diazotization, nitrosation, base-catalyzed condensation reactions, and dipolar cycloaddition reactions.…”

Investigation on Photophysical, Solvatochromism and Biological Significance of Substituted 2H‐Indazole Derivatives

“…2H-Indazole is one such heterocylic compound, which has been extensively utilized for numerous biological applications. [19][20][21][22] Indazoles are often isosteric with other classes of synthetically important 1,2-azoles. [23] Diversely substituted 2H-indazole compounds with variously substituted functional groups, possess a wide spectrum of pharmacological activities and also serve as scaffolds for many drug molecules.…”

A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions

“…The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.Molecules 2020, 25, 126 2 of 18 antipyretic, antioxidant, antiparasitic, antimicrobial, antitumoral and anti-inflammatory activities, among others [5][6][7][21][22][23].Indazoles are another important group of N-heterocycles with significant biological activities as nitric oxide synthase (NOS) inhibitors, kinase inhibitors, anti-inflammatory, anticancer, antimicrobial, antifungal, antimalarial, and antileishmanial agents, among others.Some anticancer and anti-inflammatory drugs based in indazole scaffolds are commercially available [24][25][26][27][28][29][30]. Besides the biological properties presented by indazole derivatives, this family of N-heterocycles also showed potential to be used in other fields as corrosion inhibitors, components for OLEDs and battery applications, and as copolymerizing molecules for new materials [31][32][33][34].Following our interest on developing synthetic approaches to functionalize the indazole core [35,36], we decided to follow the 1,3-dipolar cycloaddition methodology to substitute nitroindazoles with triazole or pyrazoline moieties, aiming in such way to obtain new compounds with improved biological features for different applications.…”

“…Some anticancer and anti-inflammatory drugs based in indazole scaffolds are commercially available [24][25][26][27][28][29][30]. Besides the biological properties presented by indazole derivatives, this family of N-heterocycles also showed potential to be used in other fields as corrosion inhibitors, components for OLEDs and battery applications, and as copolymerizing molecules for new materials [31][32][33][34].…”