Current Topics in Medicinal Chemistry - Volume 22, Issue 14, 2022

Indazole is a nitrogen-containing bicyclic compound, having three tautomeric forms: 1Hindazole, 2H-indazole, and 3H-indazole. Mostly, they are considered as 1H-indazole tautomeric forms, although they have the potential to tautomerism to 2H- and 3H-indazole forms. Indazoles are involved in a wide variety of biological and enzymatic processes. Therefore, they exhibit a series of pharmacological activities. Indazoles show potent activities against neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), mood disorders, etc., by inhibiting different signaling pathways and the generation of neurotransmitters and activation of enzyme activity. They effectively prevent neurological diseases by different mechanisms, such as by inhibiting the monoamine oxidase (MAO) and kinase enzymes like Glycogen synthase kinase 3 (GSK3), and leucinerich repeat kinase enzyme 2 (LRRK2). In this article, we have discussed multiple causative strategies of indazole to treat neurological diseases. This has aroused special attention in the discovery of the novel indazoles and their biological activities.

Heterocycles consisting of a nitrogen atom, Indazole, is a pungent, biological, heterocyclic, bicyclic compound possessing electron-rich portions. Indazole is composed of two nitrogen atoms put under the azoles family, further called isoindazolone. It is colorless solid nitrogen– containing heterocyclics with atomic formula-C7H6N2 are extraordinary scaffolds, still identified as isoindazole. Therefore, analogs of Indazole have experienced expert approaches in later times because of its special biological properties, such as anti-microbial, anti-inflammatory, anticancer, anti- HIV and antihypertensive actions. 1H-indazole and 2H-indazole are two toutomeric forms of Indazole. Sometimes, indazole produces three tautomeric forms that are 1H, 2H and 3H tautomers of indazole. 1H-indazole is reliable than 2H-indazole. We should note that a series of derivatives of indazole having 2H toutomers follow hybridization of cyclic systems and act as anti-inflammatory as well as anti-microbial compounds. It formed Indazole itself and derivatives of Indazole in natural products. A sequence of N-methyl-3-aryl inazoles has dominant against bacterial strains like xanthomon as campstris, Baillus cereus, Escherichia coli, Bacillus megaterium and a fungal strain candida albicans found by in-vitro anti-microbial study of indazole derivatives.

Indazole is a vital nitrogen-containing heterocyclic unit in organic and medicinal chemistry research and a helpful precursor molecule for the production of various types of encirclement heterocycles. Indazole analogues are diverse pharmacological agents that can be used to treat a variety of conditions, including cancer, inflammation, infectious diseases, and neurological problems. In fact, the indazole moiety containing inhibitors also showed excellent medicinal properties for the treatment of parasitic diseases. Therefore, the development of new inhibitors has immense promise for usage as key components for the next generation of antiparasitic medication. In this review, we have summarized the recent developments of indazole-containing antiparasitic inhibitors, specially anti-protozoal, anti-fungal, and antiamoebic inhibitors, as well as their structure-activity relationship (SAR) findings for medicinal chemists who are searching for new preclinical parasitic drug candidates.

Indazoles are a class of heterocyclic compounds with a bicyclic ring structure composed of a pyrazole ring and a benzene ring. Indazole-containing compounds with various functional groups have important pharmacological activities and can be used as structural motifs in designing novel drug molecules. Some of the indazole-containing molecules are approved by FDA and are already in the market. However, very few drugs with indazole rings have been developed against cardiovascular diseases. This review aims to summarize the structural and pharmacological functions of indazole derivatives which have shown efficacy against cardiovascular pathologies in experimental settings.

Background: In this fast-growing lifestyle, humans are in the race against time to cope up with busy schedule. Less exercise, consumption of high calorie-low fiber food and stress take us one step closer towards digestive dysfunction. Dysfunctional digestive system causes various gastrointestinal disorders like constipation, IBS, UC, diarrhea, gastrointestinal tract immobility, hyperglycemia, hemorrhoids, fistula, anal fissures, stomach cancer, hepatocellular carcinoma, pancreatic cancer, colon cancer and metabolic syndrome. Amongst various natural and synthetic indazole derivatives nigellicine, nigellamine, nigellidine, zanubrutinib and SCH772984 showed prominent results to cure various gastrointestinal disorders. Objectives: In this manuscript, we focus on the importance of indazole derivatives in the treatment of various gastrointestinal diseases. Results and Conclusion: In the treatment of IBS, four positions (R¹, R², R³ and R⁴) of indazole were mainly substituted with aromatic aldehyde/substituted methyl, aromatic acid/formamide, benzamide/ sulfonamide and methyl groups, respectively. In case of diarrhea and metabolic syndrome treatment, substitutions with benzyl/isopropyl/acetaldehyde (R1 position) and carboxamide/ formamide (R² position) of indazole play a critical role. Also, in the treatment of diabetes melitus, all six positions of indazole derivative were substituted with substituted aryl/alkyl/aromatic acid, substituted formamide, substituted acetamide/hydrazide group, halo aryl, substituted aryl/aromatic acid and a long chain of alkyl-aryl alcohol groups, respectively. In the treatment of gastrointestinal cancers, all six positions of indazole derivative were substituted with benzylamide (R¹), octanediamide/ benzamide/formamide (R²), carbaldehyde (R⁴) and substituted phenyl (R⁵ and R⁶) groups, respectively. Six receptors (6NP0, 2YME, 4EFU, 4WZ8, 5U4W and 7KKP) associated with GI disorders (co-crystallized with indazole derivative) were identified. Analysis of the receptors showed that co-crystalized ligand molecules were well-interacted with receptors via pie-pie interaction, coordinate and sigma bonding within 4 Å distance. As per Ramachandran plot analysis, more than 90% of the amino acid residues were present in the most favored region. So, if sufficient focuses are imposed on the development of newer indazole derivatives to treat gastrointestinal diseases, it will work as a boon to society.