The State of the Art of Pyrazole Derivatives as Monoamine Oxidase Inhibitors and Antidepressant/Anticonvulsant Agents

Abstract

Monoamine oxidase plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. The development of human MAO inhibitors led to important breakthroughs in the therapy of several neuropsychiatric disorders. Different families of heterocycles containing 2 or 4 nitrogen atoms have been used as scaffolds for synthesizing selective monoamine oxidase inhibitors, but the early period of the MAO-inhibitors started with hydrazine derivatives. Pyrazole, pyrazoline, and pyrazolidine derivatives can be considered as a cyclic hydrazine moiety. This scaffold also displayed promising antidepressant and anticonvulsant properties as demonstrated by different and established animal models. Diversely substituted pyrazoles, embedded with a variety of functional groups, are important biological agents and a significant amount of research activity has been directed towards this chemical class.

Brønsted Acidic Dicationic Ionic Liquid Immobilized on Fe3O4@SiO2 Nanoparticles as an Efficient and Magnetically Separable Catalyst for the Synthesis of Bispyrazoles

“…[34][35][36][37] Among various pyrazole derivatives, more specifically, 4,4'-(arylmethylene) bis (3-methyl-1-phenyl-1H-pyrazol-5-ol) has attracted considerable interest. They have a wide domain of approved biological activity such as anti-inflammatory, [38] antidepressants, [39] antibacterial, [40] antifungal, [41] antiviral, [42] and as pesticide. [43] Given such intrinsic merits, various synthetic protocols have been reported for the synthesis of 4,4'-(arylmethylene) bis (3-methyl-1-phenyl-1H-pyrazol5-ol) derivatives.…”

A density functional theory study of the stereoselectivity of Cu(OTf)2‐catalyzed [3+2] cycloaddition of trifluoromethylated N‐acylhydrazones and isoprene: A concerted asynchronous mechanism

“…Pyrazolidines and pyrazolines are highly important compounds because of their wide presence in natural products and their bioactive and unique photophysical properties. [ 1–13 ] Therefore, many experimental and theoretical works have been dedicated to the efficient and stereoselective synthesis of pyrazolidine and pyrazoline compounds. [ 14–28 ] For instance, Kobayashi found that the Lewis acid chiral zirconium/BINOL complex can be used as an efficient catalyst to synthesize entioselectively pyrazolidine products via inter‐ or intra‐molecular [3+2] cycloaddition between hydrazones and alkenes.…”

Synthesis and Evaluation of A New Series of Thiazolyl-Pyrazoline Derivatives as Cholinesterase Inhibitors

“…16,17 Diversely substituted pyrazolines embedded with a variety of functional groups have been reported to inhibit MAOs and cholinesterases, molecular targets important for the treatment of neurodegenerative disorders such as Parkinson's disease and AD. [16][17][18][19][20][21][22][23] Prompted by the aforementioned findings and in the continuation of our ongoing research on thiazoles 24 and pyrazolines 25 as cholinesterase inhibitors, we designed a new series of thiazolylpyrazoline derivatives based on the molecular hybridization of thiazole and pyrazoline scaffolds. 26 A facile and versatile synthetic route was used to prepare the title compounds and their inhibitory effects on AChE and BuChE were investigated.…”