Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

Costa, Rafael Fernades; Turones, Larissa Córdova; Cavalcante, Keilah Valéria Naves; Júnior, Ismael Aureliano Rosa; Xavier, Carlos Henrique; Rosseto, Renato; Napolitano, Hamilton B.; Castro, Patrícia; Neto, Marcos Luiz Ferreira; Galvão, Gustavo Mota; Menegatti, Ricardo; Pedrino, Gustavo Rodrigues; Costa, Élson Alves; Martins, José Luís Rodrigues; Fajemiroye, James Oluwagbamigbe

doi:10.3389/fphar.2021.666725

Cited by 72 publications

(40 citation statements)

References 77 publications

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“…A chemical entity search for pyrazole-benzylamine moieties in the Protein Data Bank (PDB) revealed that similar P1-binding moieties had already been explored, crystallized with trypsin, and incorporated into FXa inhibitors (PDB ID: 4ABE and 4ABD, 3M35, 3M36, and 3M37). Over a dozen pyrazole-containing, synthetic medicines are on the market, and even more pyrazole-containing drugs have gained regulatory approval over the past few years. − …”

Section: Results and Discussionmentioning

confidence: 99%

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)

Kotian

Vadlakonda

et al. 2021

J. Med. Chem.

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Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration’s approval for the prophylactic treatment of HAE attacks in patients 12 years and older.

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Section: Results and Discussionmentioning

confidence: 99%

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)

Kotian

Vadlakonda

et al. 2021

J. Med. Chem.

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“…In addition, the CF 3 fragment itself has additional advantages, such as increasing the lipophilicity of the compounds. The introduction of a pharmacologically important active pyrazole scaffold that possesses almost all types of pharmacological activities, including anticancer [ 48 , 49 , 50 , 51 ], to the molecule can provide additional benefits for the fluorophore. Moreover, the target compound, due to a combination of the donor (pyrazole) [ 52 ] and acceptor (phenyl) pyrrole units bonded by the trifluoromethynylene spacer, is characterized by an asymmetric structure and, hence, increased polarization and polarizability of molecules.…”

Section: Resultsmentioning

confidence: 99%

Application of meso-CF3-Fluorophore BODIPY with Phenyl and Pyrazolyl Substituents for Lifetime Visualization of Lysosomes

et al. 2022

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A bright far-red emitting unsymmetrical meso-CF3-BODIPY fluorescent dye with phenyl and pyrazolyl substituents was synthesized by condensation of trifluoropyrrolylethanol with pyrazolyl-pyrrole, with subsequent oxidation and complexation of the formed dipyrromethane. This BODIPY dye exhibits optical absorption at λab ≈ 610–620 nm and emission at λem ≈ 640–650 nm. The BODIPY was studied on Ehrlich carcinoma cells as a lysosome-specific fluorescent dye that allows intravital staining of cell structures with subsequent real-time monitoring of changes occurring in the cells. It was also shown that the rate of uptake by cells, the rate of intracellular transport into lysosomes, and the rate of saturation of cells with the dye depend on its concentration in the culture medium. A concentration of 5 μM was chosen as the most suitable BODIPY concentration for fluorescent staining of living cell lysosomes, while a concentration of 100 μM was found to be toxic to Ehrlich carcinoma cells.

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“…are appealing medicinal development targets due to their broad variety of biological activities. [1][2][3] NSAIDs are used to treat a wide variety of conditions, including rheumatoid arthritis, respiratory tract infections, fever, soft tissue lesions, and oral cavity lesions. Celecoxib 1 (Pyrazole nucleus COX-2 inhibitor) is a non-addictive anti-inflammatory and analgesic.…”

Section: Pyrazolesmentioning

confidence: 99%

Saccharomyces cerevisiae Catalyzed Synthesis and Evaluation of Pyrazoles

Rajkumar¹,

Venkata²,

Nagarajan³

2022

Ind. J. Pharm. Edu. Res

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Background: Biocatalysis in organic solvents has several benefits over aqueous solvents, including solubility of organic substrates, ease of workup, separation of the product, and, in certain cases, reusability of biocatalysts. Materials and Methods: A simple, effective, and environmentally friendly technique for synthesizing pyrazoles has been established, which involves the cyclo condensation of chalcones and isonicotinic acid hydrazide in organic solvents using a relatively inexpensive catalyst baker's yeast (Saccharomyces cerevisiae). Molecular properties prediction and docking studies were also performed. Results:The predicted molecular properties suggest that the molecules are safe for oral consumption and their docking studies on 2BVC-Mycobacterium tuberculosis glutamine synthetase show their favorable ligand binding nature. The structural assignments were validated based on spectrum data. The compounds were evaluated for their antitubercular, in vitro anti-inflammatory, and anti-oxidant effects. The analysis reveals that synthesized derivatives of pyrazoles possessing methoxy, nitro, hydroxyl, fluoro, and chloro substitution through the phenyl ring help the molecule to increase its pharmacological activities. However, the substituted thiophene ring in the side chain also facilitates the biological action of the molecules. Conclusion: Anti-inflammatory, anti-oxidant, and anti-tubercular properties are due to the presence of the pyrazole ring.

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Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

Cited by 72 publications

References 77 publications

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)

Application of meso-CF3-Fluorophore BODIPY with Phenyl and Pyrazolyl Substituents for Lifetime Visualization of Lysosomes

Saccharomyces cerevisiae Catalyzed Synthesis and Evaluation of Pyrazoles

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