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Future Medicinal Chemistry Nov 2023Pyrazole or 1-pyrazole, a five-membered 1,2-diazole, is found in several approved drugs and some bioactive natural products. A myriad number of derivatives of this small... (Review)
Review
Pyrazole or 1-pyrazole, a five-membered 1,2-diazole, is found in several approved drugs and some bioactive natural products. A myriad number of derivatives of this small molecule have been reported in clinical and preclinical studies for the potential treatment of several diseases. The number of drugs containing a pyrazole nucleus has increased significantly in the last 10 years. Some of the best-selling drugs in this class are ibrutinib, ruxolitinib, axitinib, niraparib and baricitinib, and are used to treat different types of cancers; lenacapavir to treat HIV; riociguat to treat pulmonary hypertension; and sildenafil to treat erectile dysfunction. Several aniline-derived pyrazole compounds have been reported as potent antibacterial agents with selective activity against methicillin-resistant and vancomycin-resistant enterococci. Here, we discuss the pyrazole-derived drugs reported up to September 2023.
Topics: Male; Humans; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Pyrazoles; Drug Discovery; Microbial Sensitivity Tests
PubMed: 37933613
DOI: 10.4155/fmc-2023-0207 -
Fundamental & Clinical Pharmacology Apr 2021The therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis... (Review)
Review
The therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis of the first pyrazole-antipyrine in 1887, several other derivatives have been screened for anti-inflammatory, analgesic, and antipyretic activities. Arguably, the pyrazole ring, as a major pharmacophore and central scaffold partly, defines the pharmacological profile of several derivatives. In this review, we explore the structural-activity relationship that accounts for the pharmacological profile of pyrazole derivatives and highlights future research perspectives capable of optimizing current advancement in the search for safe and efficacy anti-inflammatory drugs. The flourishing research into the pyrazole derivatives as drug candidates has advanced our understanding of inflammation-related diseases and treatment.
Topics: Anti-Inflammatory Agents; Drug Design; Humans; Inflammation; Molecular Structure; Pyrazoles
PubMed: 33171533
DOI: 10.1111/fcp.12629 -
Molecules (Basel, Switzerland) Feb 2021The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots... (Review)
Review
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).
Topics: Alzheimer Disease; Animals; Humans; Molecular Structure; Parkinson Disease; Pyrazoles
PubMed: 33668128
DOI: 10.3390/molecules26051202 -
European Journal of Medicinal Chemistry Feb 2021Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most... (Review)
Review
Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most threatening aspect is the rapid resistance development of MRSA to any approved antibiotics, including vancomycin. The development of new, efficient, and nontoxic drug candidate to fight against MRSA isolates is the need of the hour. The intriguing molecular structure and versatile bioactive pyrazole core attracting to development required novel antibiotics. This review presents the decade developments of pyrazole-containing derivatives with a broad antibacterial movement against diverged bacterial strains. In specific, we correlated the efficacy of structurally diversified pyrazole analogs against MRSA and discussed different angles of structure-activity relationship (SAR). The current survey highlights pyrazole hybrids' present scenario on MRSA studies, covering articles published from 2011 to 2020. This collective information may become an excellent platform to plan and develop new pyrazole-based small MRSA growth inhibitors with minimal side effects.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 33395624
DOI: 10.1016/j.ejmech.2020.113134 -
Organic & Biomolecular Chemistry Nov 2022Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several... (Review)
Review
Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several decades. Many transformations are now available to conveniently access pyrazoles from readily available starting materials. Conventionally, the synthesis of pyrazoles involves the condensation reaction of hydrazines with 1,3-dicarbonyl compounds or their synthetic equivalents and 1,3-dipolar cycloaddition reactions of diazo compounds with dipolarophiles. The present review provides comprehensive information on the development of synthetic approaches to access pyrazoles [3 + 2] cycloaddition reactions of diazo compounds and their synthetic equivalents.
Topics: Cycloaddition Reaction; Azo Compounds; Pyrazoles; Hydrazines
PubMed: 36331498
DOI: 10.1039/d2ob01918c -
Mini Reviews in Medicinal Chemistry 2022The search for new anticancer agents is considered a dynamic field of medicinal chemistry. In recent years, the synthesis of compounds with anticancer potential has... (Review)
Review
The search for new anticancer agents is considered a dynamic field of medicinal chemistry. In recent years, the synthesis of compounds with anticancer potential has increased and a large number of structurally varied compounds displaying potent anticancer activities have been published. Pyrazole is an important biologically active scaffold that possesses nearly all types of biological activities. The aim of this review is to collate literature work reported by researchers to provide an overview on in vivo and in vitro anticancer activities of pyrazole based derivatives among the diverse biological activities displayed by them and also to present recent efforts made on this heterocyclic moiety regarding anticancer activities. This review has been driven by the increasing number of publications on this issue, which have been reported in the literature since the end of the 20 century (from 1995-to date).
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Pyrazoles; Structure-Activity Relationship
PubMed: 33823764
DOI: 10.2174/1389557521666210325115218 -
Molecules (Basel, Switzerland) Jul 2023The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases... (Review)
Review
The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases inhibitors (PKI) is the best available option for the cure of cancer. The pyrazole ring is extensively employed in the field of medicinal chemistry and drug development strategies, playing a vital role as a fundamental framework in the structure of various PKIs. This scaffold holds major importance and is considered a privileged structure based on its synthetic accessibility, drug-like properties, and its versatile bioisosteric replacement function. It has proven to play a key role in many PKI, such as the inhibitors of Akt, Aurora kinases, MAPK, B-raf, JAK, Bcr-Abl, c-Met, PDGFR, FGFRT, and RET. Of the 74 small molecule PKI approved by the US FDA, 8 contain a pyrazole ring: Avapritinib, Asciminib, Crizotinib, Encorafenib, Erdafitinib, Pralsetinib, Pirtobrutinib, and Ruxolitinib. The focus of this review is on the importance of the unfused pyrazole ring within the clinically tested PKI and on the additional required elements of their chemical structures. Related important pyrazole fused scaffolds like indazole, pyrrolo[1,2-b]pyrazole, pyrazolo[4,3-b]pyridine, pyrazolo[1,5-a]pyrimidine, or pyrazolo[3,4-d]pyrimidine are beyond the subject of this work.
Topics: Pyrazoles; Protein Kinase Inhibitors; Antineoplastic Agents; Drug Design; Structure-Activity Relationship; Humans; Animals
PubMed: 37513232
DOI: 10.3390/molecules28145359 -
Bioorganic Chemistry Oct 2023Tumor selectivity is yet a challenge in chemotherapy-based cancer treatment. A series of calixarenes derivatized at the lower rim with 3-phenyl-1H-pyrazole units with...
Tumor selectivity is yet a challenge in chemotherapy-based cancer treatment. A series of calixarenes derivatized at the lower rim with 3-phenyl-1H-pyrazole units with variable upper-rim substituent and conformations of macrocyclic core, alkyl chain length between heterocycle and core, as well as phenolic monomer (5-(4-tert-butylphenyloxy)methoxy-3-phenyl-1H-pyrazole) have been synthesized and characterized in a range of therapeutically relevant cellular models (M-HeLa, MCF7, A-549, PC3, Chang liver, and Wi38) from different target organs/systems. Specific cytotoxicity for M-HeLa cells has been observed in tert-butylcalix[4]arene pyrazoles in 1,3-alternate (compound 7b) and partial cone (compound 7c) conformations with low mutagenicity and haemotoxicity and in vivo toxicity in mice. Compounds 7b,c have induced mitochondrial pathway of apoptosis of M-HeLa cells through caspase-9 activation preceded by the cell cycle arrest at G0/G1 phase. A concomitant overexpression of DNA damage markers in pyrazole-treated M-HeLa cells suggests that calixarene pyrazoles target DNA, which was supported by the presence of interactions between calixarenes and ctDNA at the air-water interface.
Topics: Animals; Humans; Mice; Calixarenes; HeLa Cells; Neoplasms; Porifera; Pyrazoles
PubMed: 37480816
DOI: 10.1016/j.bioorg.2023.106742 -
European Journal of Medicinal Chemistry 2013Pyrazole has been the topic of interest for thousands of researchers across the world because of its wide spectrum pharmacological activities. Various structural... (Review)
Review
Pyrazole has been the topic of interest for thousands of researchers across the world because of its wide spectrum pharmacological activities. Various structural modifications of the pyrazole nucleus have been made to explore its characteristics and biological potential. The present work aims to review the use of molecular modeling in the designing of novel pyrazole analogs that may target various receptors such as protein kinase inhibitor, tyrosine kinase, Aurora-A kinase, tumor growth factor (TGF), cyclin dependent kinase (CDK) and fibroblast growth factor (FGF), which are significant for the management of cancer. An insight has been given in this article for the importance of pyrazoles in the treatment of cancer and the perspectives that they hold for future research.
Topics: Animals; Antineoplastic Agents; Humans; Models, Molecular; Neoplasms; Pyrazoles
PubMed: 24161702
DOI: 10.1016/j.ejmech.2013.10.004 -
European Journal of Medicinal Chemistry Oct 2017One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium... (Review)
Review
One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles. Numerous of pyrazole-containing derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency and may have novel mechanism of action. This review aims to outline the recent achievements in pyrazole-containing derivatives as anti-TB agents and their structure-activity relationship.
Topics: Antitubercular Agents; Dose-Response Relationship, Drug; Humans; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship; Tuberculosis
PubMed: 28818767
DOI: 10.1016/j.ejmech.2017.07.059