Pyrazole Scaffold Synthesis, Functionalization, and Applications in Alzheimer’s Disease and Parkinson’s Disease Treatment (2011–2020)

Abstract

The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011–2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer’s disease (AD) and Parkinson’s disease (PD).

Design, synthesis, characterization,in vitroscreening, molecular docking, 3D-QSAR, and ADME-Tox investigations of novel pyrazole derivatives as antimicrobial agents

“…19–21 The synthesis of new pyrazole derivatives and the study of their chemical and biological behavior have aroused great interest in recent years, which is reflected by the large number of published studies. 22–26 In fact, pyrazole derivatives possess remarkable pharmacological properties such as anti-inflammatory, 24 antibacterial, 15 antifungal, 25 antitubercular, 26 anticancer, 27 anti-Alzheimer's activity, 28 etc. It has become, therefore, necessary to intensify research in this field, knowing that nitrogen heterocycles remain a fruitful source for the pharmaceutical and medicinal industries.…”

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

“…These molecules are: celecoxib and lonazolac, approved COX-2 inhibitor drugs [6,7]; crizotinib [8], an anticancer drug; sildenafil [8] (Viagra), a PDE5 inhibitor; zometapine [9], an antidepressant; lorediplon A, used for the treatment of insomnia [10]; anagliptin E, an inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus [11] (Figure 2); and many others. Furthermore, their derivatives are reported to possess antimicrobial [12][13][14], antiviral [15][16][17], antidiabetic [18,19], anti-Alzheimer [20,21], antitubercular [22,23], and antileishmanial [24] properties, as well as α-glucosidase inhibitory activity [25]. In this context, the pyrazole scaffold is an adaptable molecule that has attracted the interest of medicinal chemists due to its wide range of various pharmacological activities, being a structural motif present in several drug molecules.…”

Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors

“…In this context, the pyrazole scaffold is a versatile molecule that has attracted attention due to its wide range of diverse pharmacological activities, which make it a versatile lead molecule in several drug molecules such as celecoxib, ramifenazone, lonazolac, and rimonabant, drugs approved as COX-2 inhibitors [13][14][15][16], crizotinib [17] and paropanib [17] as anticancer drugs, sildenafil [17] (Viagra) PDE5 inhibitor, zometapine [18] as antidepressant, ocinaplon [19] as anxiolytic (Figure 1), and many others. Additionally, in recent years, their derivatives have been reported to possess antimicrobial activity [20][21][22] as well as antiviral [23,24], antidiabetic [25,26], anti-Alzheimer [27,28], antitubercular [29,30], and antileishmanial properties [31]. In this context, the pyrazole scaffold is a versatile molecule that has attracted attention due to its wide range of diverse pharmacological activities, which make it a versatile lead molecule in several drug molecules such as celecoxib, ramifenazone, lonazolac, and rimonabant, drugs approved as COX-2 inhibitors [13][14][15][16], crizotinib [17] and paropanib [17] as anticancer drugs, sildenafil [17] (Viagra) PDE5 inhibitor, zometapine [18] as antidepressant, ocinaplon [19] as anxiolytic (Figure 1), and many others.…”

“…In this context, the pyrazole scaffold is a versatile molecule that has attracted attention due to its wide range of diverse pharmacological activities, which make it a versatile lead molecule in several drug molecules such as celecoxib, ramifenazone, lonazolac, and rimonabant, drugs approved as COX-2 inhibitors [13][14][15][16], crizotinib [17] and paropanib [17] as anticancer drugs, sildenafil [17] (Viagra) PDE5 inhibitor, zometapine [18] as antidepressant, ocinaplon [19] as anxiolytic (Figure 1), and many others. Additionally, in recent years, their derivatives have been reported to possess antimicrobial activity [20][21][22] as well as antiviral [23,24], antidiabetic [25,26], anti-Alzheimer [27,28], antitubercular [29,30], and antileishmanial properties [31]. Our aim was to further support our previous studies on hCAs as valid and robust pharmacological targets for the treatment of different pathological conditions that are characterized by the overexpression of different human CA isoforms such as CA IX and XII over the ubiquitous hCA I and hCA II in order to decrease the side effects due to their inhibition, such as with the clinically approved drug acetazolamide (AAZ) depicted in Figure 2.…”