Indazole

Introduction

Indazole are a kind of aromatic heterocyclic compounds, first defined by scientist Emil Fisher as a “pyrazole ring fused with the benzene ring”. There are two tautomeric forms of indazole can be discussed, the 1H- and 2H-form. It has been extensively explored resulting from its intriguing chemical and biological properties. Indazoles occur rarely in natural environment. To date, only three natural products possessing the indazole ring have been isolated, namely, Nigellicine, Nigeglanine, and Nigellidine whereas the great majority of indazole derivatives are produced by organic synthetic methods.

IndazoleFig. 1 Tautomers of indazole and naturally accruing indazole moiety.

Indazole and the simple alkylindazoles are white crystalline solids. The indazole ring possesses two nitrogen atoms and can be functionalized with high selectivity at different positions. Its planarity, side chain length and fictionalizations at different positions can afford an enormous number of indazole derivatives, providing new molecules with biological and therapeutic properties.

Applications

Pharmaceutical Chemistry:

A large number of synthetically prepared indazoles derivatives have displayed biological and pharmacological properties. Such as Bendazac (12) is a non-steroidal anti-inflammatory agent, used as an anti-cataract drug. New YC-1 indazole derivative (13) were synthesized and evaluated with HIF-1 transcriptional activity, in vivo. Furthermore, for the mechanistic study of the YC-1 derivatives, shows the anti-proliferative activity against human cancer cells and 1, 3, 5-trisustituted indazole derivative (14) as an extremely potent antioxidant. Recently it has been reported that a combination of lonidamine (15) was shown to have antitumor properties in phaseII and phase-III studies for the treatment of advanced breast, ovarian and lungs cancer are encouraging. The 7-nitro indazoles derivative (16) was tested for the treatment of alcohol dependence, anti-mutagenesis and anti-oxidant properties. Similarly, piperidine derivative of indazole (17) has been patented as a non-narcotic, analgesic and antipsychotic drug.

Indazole Fig. 2 Drug molecules containing indazole moiety (Eur. J. Med. Chem., 2015, 90, 707-731.)

Agriculture:

Indazole ring-based compounds have also been reported in herbicides and their effect on plant growth has been studied. 1H-indazole is a herbicide and behaves like a growth inhibitor. 1H-indazole and its derivatives show inhibition when applied in soil before or after seed germination; this inhibition can be helpful in removing undesired weeds in the paddy field without any material phytotoxicity. They have high herbicidal potency, especially on broad-leaved weeds like false pimpernel, Indian tooth cup, water wort, and graminaceous weeds such as barnyard grass.

Fluorescent Material:

Indazole nucleus has become of interest as a key moiety of dyes and fluorescent compounds, which can be tuned to wide range of emissions.

Indazole Fig. 4 indazole-based fluorescence dyes with different emissions

Organic Synthesis:

Indazoles can be transformed to indazoliums halide, which has been applied in the palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of aryl bromides with arylboronic acids at mild reaction conditions.

Indazole Fig. 3 ligand of palladium catalysts (Tetrahedron, 2016, 72, 2632-2636)

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