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European Journal of Medicinal Chemistry Jun 2015Pyrazole is a five membered and two-nitrogen containing heterocyclic ring. These structures have been investigated in the development of novel compounds with... (Review)
Review
Pyrazole is a five membered and two-nitrogen containing heterocyclic ring. These structures have been investigated in the development of novel compounds with hypoglycemic, analgesic, anti-inflammatory, antimicrobial, anticonvulsant, antidepressant, antimycobacterial, antioxidant, antiviral, insecticidal and antitumor activities. Therefore, these compounds have been synthesized as target structures by many researchers and were evaluated for their biological activities. We hope that the bioactivity of pyrazole derivatives will be beneficial for the rational design of new generation of small molecule drugs. In this review, we report the structures of 1H-pyrazoles with their corresponding biological activities for 21st (in 2000-2014 years) century.
Topics: Animals; Drug Discovery; Humans; Pyrazoles
PubMed: 25555743
DOI: 10.1016/j.ejmech.2014.11.059 -
Nature Jun 1951
Topics: Guanidine; Pyrazoles
PubMed: 14843169
DOI: 10.1038/1671037a0 -
Bioorganic & Medicinal Chemistry Letters Aug 2015Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity...
Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors.
Topics: Arachidonate 15-Lipoxygenase; Benzoxazoles; Humans; Lipoxygenase Inhibitors; Pyrazoles; Structure-Activity Relationship; Triazoles
PubMed: 26037322
DOI: 10.1016/j.bmcl.2015.05.004 -
European Journal of Medicinal Chemistry Nov 2008We have previously described a series of 4,5-dihydro-1H-pyrazole as moderately potent nNOS inhibitors. As a follow up of these studies, we report here the preparation...
We have previously described a series of 4,5-dihydro-1H-pyrazole as moderately potent nNOS inhibitors. As a follow up of these studies, we report here the preparation and the preliminary evaluation of a series of 1-alkyl-3-benzoyl-4,5-dihydro-1H-pyrazole and 1-alkyl-3-benzoyl-1H-pyrazole as potential inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS). None of the reported compounds exhibited significant iNOS or nNOS inhibition, although the 1-benzyl-3-(2-amino-5-chlorobenzoyl)-1H-pyrazole-5-carboxylic acid ethyl ester derivative (10l), which shows an inhibition of 50% versus iNOS at a 1mM final concentration and no activity against nNOS, is potentially amenable of further optimization. The reasons for the inactivity of the reported series are discussed on the basis of docking studies.
Topics: Alkylation; Animals; Enzyme Inhibitors; Male; Models, Molecular; Molecular Structure; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Protein Binding; Pyrazoles; Rats; Rats, Wistar; Structure-Activity Relationship
PubMed: 18325637
DOI: 10.1016/j.ejmech.2008.01.014 -
Canadian Journal of Physiology and... Jul 2020Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant...
Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1-pyrazol (), 3,5-dimethyl-4-(phenylselanyl)-1-pyrazole (), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1-pyrazole (), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1-pyrazole (), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1-pyrazole (), 3,5-dimethyl-4-(phenylthio)-1-pyrazole (), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1-pyrazole (), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1-pyrazole (), and 3,5-dimethyl-1-phenyl-1-pyrazole (). In vitro, 4-(arylcalcogenyl)-1-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds , , and presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds and presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds , , and (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds , , and did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.
Topics: Administration, Oral; Animals; Cerebral Cortex; Drug Evaluation, Preclinical; Free Radical Scavengers; Kidney; Lipid Peroxidation; Liver; Male; Mice; Models, Animal; Pyrazoles; Reactive Oxygen Species; Selenium; Sulfur; Toxicity Tests, Acute
PubMed: 32597688
DOI: 10.1139/cjpp-2019-0356 -
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 -
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 -
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 -
European Journal of Medicinal Chemistry Jul 2014A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (15-24) were evaluated for their affinity to CB2 and CB1 cannabinoid...
A new series of 1H-benzofuro[3,2-c]pyrazole-3-carboxamides was synthesized. The novel compounds (15-24) were evaluated for their affinity to CB2 and CB1 cannabinoid receptors. The synthesis of the title compounds takes advantage of the acid-catalysed thermal cyclization of bicyclic hydrazone ethyl 2-(2-(2,4-dichlorophenyl)hydrazono)-2-(6-methyl-3-oxo-2,3-dihydrobenzofuran-2-yl)acetate to tricyclic ethyl 1-(2,4-dichlorophenyl)-6-methyl-1H-benzofuro[3,2-c]pyrazol-3-carboxylate. All the obtained derivatives showed high affinity to CB2 receptors. Moreover, significant selectivity for CB2 over CB1 receptors was highlighted for lead derivatives amongst the novel series. The best binding profiles were determined for homologues bearing monocyclic and bicyclic monoterpenic substituents at the carbamoyl group at 3 position of the pyrazole ring (KiCB2 < 4 nM). In particular, the isopinocampheyl-substituted derivative 22 exhibited the highest selectivity for CB2 receptors with Ki values of 3.7 and 2398 nM for CB2 and CB1 receptors, respectively. Preliminary functional assays evidenced CB2 agonism behaviour for all the assayed novel derivatives.
Topics: Benzofurans; Cell Line, Tumor; Dose-Response Relationship, Drug; HL-60 Cells; Humans; Ligands; Molecular Structure; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Structure-Activity Relationship
PubMed: 24922543
DOI: 10.1016/j.ejmech.2014.05.055 -
Molecules (Basel, Switzerland) Dec 2015With the objective of finding valuable herbicidal candidates, a series of new 5-heterocycloxy-3-methyl-1-substituted-1H-pyrazoles were synthesized and their herbicidal...
With the objective of finding valuable herbicidal candidates, a series of new 5-heterocycloxy-3-methyl-1-substituted-1H-pyrazoles were synthesized and their herbicidal activities were evaluated. The bioassay results showed that some compounds exhibited excellent herbicidal activities at the concentration of 100 mg/L, and compound 5-chloro-2-((3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)oxy)pyrimidine showed bleaching activity to green weeds. In greenhouse conditions, this compound also showed excellent post-emergence herbicidal effect against Digitaria sanguinalis L. at the dosage of 750 g a. i. ha(-1).
Topics: Herbicides; Molecular Structure; Plant Weeds; Pyrazoles; Structure-Activity Relationship
PubMed: 26712728
DOI: 10.3390/molecules21010039