The Structure ofN‐phenyl‐pyrazoles and Indazoles: Mononitro, Dinitro, and Trinitro Derivatives

Abstract

This review explores the heterocyclic family of N‐nitrophenyl pyrazoles and indazoles covering mainly their structural aspects, with special emphasis on the X‐ray diffraction data. NMR spectroscopy and the theoretical calculations will also be briefly summarized. The synthesis and reactivity aspects will be reported when they are specific to these compounds.

Study of the Addition Mechanism of 1H-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions

“…The structure, tautomerism, and reactivity of 1e are of interest because of its unique ability to inhibit both MAO-B and nNOS, two biologically important enzyme systems. Furthermore, its general use as an investigative drug to study the inhibition of nNOS makes the structural study of this molecule very relevant. , This compound is the first reported indazole where both tautomers have been observed and the second in which spin–spin coupling constants with H1 have been observed observed and determined.…”

“…Some nitro-1 H -indazoles, bearing or not other C-substituents, are powerful inhibitors of nitric oxide synthase isoforms, nNOS, iNOS, and eNOS . Of the five possible C-nitro-1 H -indazoles, 3-, 4-, 5-, 6-, and 7-, only 7-nitro-1 H -indazoles (7-nitro, 3-bromo-7-nitro, and 3,7-dinitro) have inhibitory properties. − …”

“…In 1986, the reaction was carried out in neutral conditions (ethanol). 16 In 2004, 17 the reaction of indazole 1a in acid conditions was re-examined; B3LYP/6-311++G(d,p) calculations indicated that the 1-substituted isomer (2a) was 20 kJ•mol −1 more stable than the 2-substituted isomer (3a) (Scheme 2), and the NMR data were extended to 13 C and 15 N nuclei together with GIAO calculations of absolute shieldings.…”

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].…”