**2. Applications of pyrazole scaffold**

Pyrazole moiety have wide applications and are effective therapeutic scaffolds that display a wide range of biological actions as listed in **Figure 3**.

The synthesis of a novel, powerful family of 5-reductase and aromatase inhibitors derived from 1, 2, 3-triazole derivative uses pyrazole-4-carbaldehyde as the starting material. The appropriate Schiff bases were created by condensation of the starting material with active methylene and various amino pyrazoles. In contrast, starting material was treated in a single pot with ethyl cyanoacetate and thiourea to produce pyrazolo-6-thioxopyridin-2-[3H]-one. Additionally, beginning chemical was reacted with p-methoxy acetophenone, which then reacted with each of the ethyl cyanoacetates to create an unsaturated chalcone derivative. The following derivatives showed 5-α reductase inhibitor and aromatase inhibitor activity prominently

**Figure 3.** *Biological activity of pyrazole moiety.*

compared to reference drug. It is due to the pyridine moiety was present and it was connected to the pyrazoline and 1, 2, 3-trizole moieties (**Figure 4**) [47].

Sequence of pyrazolinyl and pyrazolyl pregnenolones were produced and their ability for both series to inhibit 5- α reductase was examined by multiple step synthesis and pregnenolone used as starting material. Cyclization reaction was found to be main step in this synthesis. Derivatives 4b, 4c and 6b were found to be more active for this activity as it contains fluoro group and para position chloro group. 4b and 4c contain Ar ring as follows (**Figures 5** and **6**) [48].

Khalillulha H et al. synthesized pyrazole derivatives covering 1, 4-dioxane ring which have low-molecular-weight molecules that are simple to manufacture. On the other hand, silybin is a complicated, highly molecular substance that is difficult to manufacture. In addition, the substances are anticipated to be easily metabolizable, in contrast to silybin, which is straightforward and has a low molecular

**Figure 4.** *Potent derivative showing 5- α reductase inhibitor activity.*

**Figure 5.** *Potent compound of pyrazolinyl pregnenolone.*

**Figure 6.** *6b derivatives of pyrazolyl pregnenolone.*

weight. These derivatives were prepared by Claisen–Schmidt condensation reaction using substituted acetophenone chalcones. Rats' liver damage caused by CCl4 was used in a hepatotoxicity investigation (**Figure 7**) [49].

MAO enzyme having EC number 1.4.3.4 that contain flavin Hence inhibitory activity was done by different researchers like Chimenti F et al. synthesized 1-Thiocarbamoyl-3, 5-diaryl-4, 5-dihydro-(1H) - pyrazole Derivatives by using

**Figure 7.** *Pyrazoline derivative.*

*Pyrazole Scaffold: Strategies toward the Synthesis and Their Applications DOI: http://dx.doi.org/10.5772/intechopen.108764*

chalcones, thiosemicarbazide with potassium hydroxide in ethanol as solvent. Its isomers were also tested for MAO inhibitory action. Substrate used was kynuramine. Derivative containing following group those are highly active for MAO inhibition. To check bonding affinity for MAO computational methods were also carried out. Following derivative shows potent activity (**Figure 8**) [50].

Secci D prepared pyrazole derivatives are produced either by intermolecular [3 + 2] cycloadditions of 1, 3-dipoles to alkynes excellent inhibitory effect primarily against MAO-B contain halo group when placed in the para position of the aryl group (**Figure 9**) [51].

Alam MS et al. used schiff base ligand 4-amino-1, 5-dimethyl-2-phenylpyrazole-3 one with benzaldehyde to form single crystal which was checked by X-ray diffraction analysis. For detection of antioxidant activity they used DPPH Radical Scavenging Activity assayed by Blois method (**Figure 10**) [52].

Gressleri, A et al. prepared derivatives by refluxing for 24 hours with the use of 1, 5-diarylpenta-1, 4-dien-3-ones, aminoguanidine hydrochloride, triethylamine, and ethanol. For antioxidant activity DPPH was used and the color of the DPPH shifts from violet to yellow. From all the synthesized derivatives 1-carboxyamidino-1*H*pyrazole derivatives showed potent activity. [53] Hanam A et al. made an effort to produce new heterocycles, 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl) acryloyl chloride was subjected to reactions with various mono-, 1,2-, 1,3-,1,4-, and 1,5 binucleophiles. Assay was performed by using ABTS [2, 20 -azinobis-(3-

**Figure 8.** *Pyrazole derivatives.*

**Figure 9.** *Cycloaddition derivative.*

**Figure 10.** *Pyrazole Schiff base derivative.*

**Figure 11.** *Structure of tetrazine.*

ethylbenzthiazoline-6-sulphonic acid)] method. In that comparison was done by ascorbic acid as standard (**Figure 11**) [54, 55].

Alsayari A, et al. prepared pyrazole derivatives by A sulforhodamine B assay method which was used to assess the antiproliferative effects on cancer cell lines were identified: hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116), and breast cancer (MCF-7). These are effective xanthine oxidase inhibitory action (IC50 0.83 M) and a high IC50 against the human colon cancer cell line (**Figure 12**) [56].

Different anticancer activity showing in pyrazole moiety were listed here, the preclinical or early-phase clinical trials for these described drugs were passed (**Figure 13**) [57].

Three different breast cancer cell lines, such as MDA-MB-231, MCF-7, and 4 T1, all were used by authors for breast cancer cell line study as well as HepG2 liver cancer cells, were used to test the cytotoxicity of pyrazole. Synthesized pyrazole 13 derivative (5-oxo-N<sup>0</sup> -(2-oxoindolin-3-ylidene)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbothiohydrazide), mechanism was discussed as caused 4 T1 cells to die by preventing wound healing and colony formation, delaying the G0/G1 phase of the cell cycle, activating p27 levels, and most likely inducing apoptosis through DNA intercalation. IC50 value of this synthesized derivative was found to be 25 � 0.4 μm (**Figure 14**) [58].

Human lung carcinoma A549 cells, murine P388 leukemia cells, and human ovarian adenocarcinoma A2780 cells were all tested with pyrazole derivatives by synthesizing this derivatives 2-pyridinyl moiety containing compound 12 is mostly active as shown below (**Figure 15**) [59].

Cyclin-dependent kinases (CDKs), a subfamily of the protein kinase which control the cell cycle. Given that cyclin E is selective for CDK2 and the dysregulation of particular cancer types, CDK2 is an alluring target for malignancies with particular genotypes. According to the ongoing clinical trials, CDKs inhibitor, specifically CDK2/ cyclin A-E, has the potential to be a reliable cancer target. The majority of the pyrazole scaffolds have demonstrated CDK2 inhibitor selectivity and potency [60, 61]. The antibacterial activity of a series of 1H-pyrazole-3-carboxylic acid derivatives against Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Pseudomonas putida were assessed by Akbas et al. Having antibacterial action against both Gram-positive

**Figure 12.** *Pyrazole derivative as anticancer.*

*Pyrazole Scaffold: Strategies toward the Synthesis and Their Applications DOI: http://dx.doi.org/10.5772/intechopen.108764*

**Figure 13.** *Pyrazole derivative in preclinical study.*

**Figure 15.** *Pyrazole 12 derivative.*

and Gram-negative bacteria, the results revealed that compound 5c was the best compound in the series (**Figure 16**) [62].

For the detection of pyrazole pesticides such as fibronil in water samples of environment, method solid-phase extraction (SPE) approach combining with highperformance liquid chromatography as adsorbent multi-walled carbon nanotubes was developed by Ma Jiping et al. [63] (**Figure 17**).

An essential scaffold is 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5 carbohydrazide, which is produced by Wang Y et al. as an insecticidal compounds. By using species *Helicoverpa armigera* and *Plutella xylostella* as standard tebufenozide. Fluoro group containing compound showed potent activity at fourth position and decreased by iodo group [64] (**Figure 18**).

**Figure 16.** *5C (Pyrazole carboxylate derivative).*

**Figure 18.** *Pyrazole derivative.*
