51516-67-7

Usage

Chemical Properties

White to off-white crystalline powder

InChI:InChI=1/C10H7ClN4/c11-8-1-3-9(4-2-8)15-10(13)7(5-12)6-14-15/h1-4,6H,13H2

Upstream product

• 1073-69-4 N-4-chlorophenylhydrazine 
• 123-06-8 Ethoxymethylenemalononitrile 
• 1073-70-7 4-chlorophenylhydrazine hydrochloride 
• 122-51-0 orthoformic acid triethyl ester 
• 109-77-3 malononitrile 
• 86240-43-9 (ethoxymethylene)malononitrile 
• 106-47-8 4-chloro-aniline 

Downstream Products

• 6289-01-6 4-amino-1-(4-chloro-phenyl)-1,7-dihydro-pyrazolo[3,4-d]pyrimidin-6-one 
• 50427-79-7 5-amino-1-(4-chlorophenyl)-1H-pyrazole-4-carboxamide 
• 135108-53-1 4-Amino-1-(4-chloro-phenyl)-5-methyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-6-one 
• 14678-97-8 2-(4-chloro-phenyl)-2H-pyrazol-3-ylamine 
• 77746-66-8 5-Amino-1-(4-chloro-phenyl)-1H-pyrazole-4-carbaldehyde 
• 77746-83-9 N-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-formamide 
• 77746-93-1 1-(4-Chloro-phenyl)-1H-pyrazolo[3,4-d]pyrimidine 
• 77746-79-3 [2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-[1-piperidin-1-yl-meth-(E)-ylidene]-amine 
• 77746-70-4 2-(4-Chloro-phenyl)-4-cyclopenta-2,4-dienylidenemethyl-2H-pyrazol-3-ylamine 
• 77746-96-4 1-(4-Chloro-phenyl)-1H-pyrazolo[3,4-d]pyrimidine 5-oxide 
• 77746-65-7 1-(4-Chloro-phenyl)-5-{[1-piperidin-1-yl-meth-(E)-ylidene]-amino}-1H-pyrazole-4-carbaldehyde 
• 77746-68-0 N'-[2-(4-Chloro-phenyl)-4-cyclopenta-2,4-dienylidenemethyl-2H-pyrazol-3-yl]-N,N-dimethyl-formamidine 
• 77746-97-5 1-(4-chlorophenyl)-5-dimethylaminomethyleneamino-4-phenyl-iminomethylenepyrazole 
• 77775-31-6 C₁₄H₁₆ClN₇O 

Relevant academic research and scientific papers

Synthesis of pyrazole-carboxamides and pyrazole-carboxylic acids derivatives: Simple methods to access powerful building blocks

Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.

Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase

The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC50 values of 7.0, 17.0, 13.5, and 1.0 μM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC50 values of 0.10 μM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

New pyrazolopyrimidine derivatives as Leishmania amazonensis arginase inhibitors

Arginase performs the first enzymatic step in polyamine biosynthesis in Leishmania and represents a promising target for drug development. Polyamines in Leishmania are involved in trypanothione synthesis, which neutralize the oxidative burst of reactive oxygen species (ROS) and nitric oxide (NO) that are produced by host macrophages to kill the parasite. In an attempt to synthesize arginase inhibitors, six 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents at the 4-position of the phenyl group were synthesized. All compounds were initially tested at 100 μM concentration against Leishmania amazonensis ARG (LaARG), showing inhibitory activity ranging from 36 to 74%. Two compounds, 1 (R=H) and 6 (R=CF3), showed arginase inhibition >70% and IC50 values of 12 μM and 47 μM, respectively. Thus, the kinetics of LaARG inhibition were analyzed for compounds 1 and 6 and revealed that these compounds inhibit the enzyme by an uncompetitive mechanism, showing Kis values, and dissociation constants for ternary complex enzyme-substrate-inhibitor, of 8.5 ± 0.9 μM and 29 ± 5 μM, respectively. Additionally, the molecular docking studies proposed that these two uncompetitive inhibitors interact with different LaARG binding sites, where compound 1 forms more H-bond interactions with the enzyme than compound 6. These compounds showed low activity against L. amazonensis free amastigotes obtained from mice lesions when assayed with as much as 30 μM. The maximum growth inhibition reached was between 20 and 30% after 48 h of incubation. These results suggest that this system can be promising for the design of potential antileishmanial compounds.

A Convenient Synthesis of Pyrazole-imidazoline Derivatives by Microwave Irradiation

A series of 28 hybrids pyrazole-imidazolines 1a–n and 2a–n were synthesized by a new methodology using microwave irradiation, in short time (20–30?min), in low power (50–70?W), and in 34–92% yield. Among all methodologies evaluated, no side products were obtained. All derivatives were completely characterized by FT–IR, 1H and 13C NMR, GC–MS, and HRMS.

Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease

Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluated the biological effect of pyrazole-imidazoline (1a-i) and pyrazole-tetrahydropyrimidine (2a-i) derivatives against relevant clinical forms of Trypanosoma cruzi. The structure-activity relationship (SAR), drug-target search, physicochemical and ADMET properties of the major active compounds in vitro were also assessed in silico. Pyrazole derivatives showed no toxicity in Vero cells and also no cardiotoxicity. Phenotypic screening revealed two dichlorinated pyrazole-imidazoline derivatives (1c and 1d) with trypanocidal activity higher than that of benznidazole (Bz) against trypomastigotes; these were also the most potent compounds against intracellular amastigotes. Replacement of imidazoline with tetrahydropyrimidine in the pyrazole compounds completely abolished the trypanocidal activity of series 2(a-i) derivatives. The physicochemical and ADMET properties of the compounds predicted good permeability, good oral bioavailability, no toxicity and mutagenicity of 1c and 1d. Pyrazole nucleus had high frequency hits for cruzipain in drug-target search and structure activity relationship (SAR) analysis of pyrazole-imidazoline derivatives revealed enhanced activity when chlorine atom was inserted in meta-positions of the benzene ring. Additionally, we found evidence that both compounds (1c and 1d) have the potential to interact non-covalently with the active site of cruzipain and also inhibit the cysteine proteinase activity of T. cruzi. Collectively, the data presented here reveal pyrazole derivatives with promise for further optimization in the therapy of Chagas disease.

Synthesis and anti-Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives

Nine 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents in the 4-position of the phenyl group and benzenesulfonamide moiety were synthesized and evaluated against Plasmodium falciparum. Six compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 5.13 to 12.22 μM. The most active derivative with substituents R1 = F / R2 = CH3 exhibited an IC50 value of 5.13 μM and an IS value of 62.90, which was higher than that of the control drug sulfadoxine. For this reason, it is possible to conclude that the 1H-pyrazolo[3,4-d]pyrimidine system is promising as a prototype for further studies of antimalarial candidates.

Novel coumarin-pyrazole carboxamide derivatives as potential topoisomerase II inhibitors: Design, synthesis and antibacterial activity

The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella. The selected compounds (8III-k, 8V-c and 8V-k) exhibit potent inhibition against Topo II and Topo IV with IC50 values (9.4–25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Topo II inhibiting bactericides.

Design, synthesis, and antifungal activity of novel cinnamon–pyrazole carboxamide derivatives

(Table presented.). To discover succinate dehydrogenase inhibitors with a novel structure, we introduced cinnamic acid structure to optimize the lead structure 1 and synthesized four series of cinnamon–pyrazole carboxamide derivatives. The bioassay data showed that compounds (E)-N-(1-[4-chlorophenyl]-4-cyano-1H-pyrazol-5-yl)-3-(2-fluorophenyl) acrylamide (5III-d) and (E)-3-(2-chlorophenyl)-N-(1-[4-chlorophenyl]-4-cyano-1H-pyrazol-5-yl) acrylamide (5III-f) showed the significant antifungal activity against three fungi. In addition, 5III-d and 5III-f exhibited the excellent inhibitory effect against succinate dehydrogenase (SDH) enzymes with IC50 values ranging from 19.4 to 28.7 μM. The study demonstrates that the chlorine substituent group is present on both the phenyl and pyrazole rings that have a very good effect on the antifungal effect, and the compounds 5III-d and 5III-f can act as potential SDH inhibitors (SDHI) and throw a sprat for a new generation of SDHI.

Synthesis and biological evaluation of new tacrine analogues under microwave irradiation

Efficient routes to various kinds of heterocycles incorporating the p-halophenyl moiety have been synthesized. Different pyrrole derivatives have been synthesized, as well, by Thorpe–Ziegler cyclization. Therefore, we synthesized different analogues of tacrine by Friedl?nder reaction of o-amino nitriles (pyrazolo, furano and pyrrolo) with different cycloalkanones. The use of microwave irradiation leads to shorter production times and high product conversion. These synthesized compounds were biologically evaluated by Ellman’s test on acetylcholinesterase inhibition.

Synthesis and Biological Activity of Amide Compounds Containing Pyrazole Mandelic Acid Groups

A series of novel mandelic acid pyrazole amide compounds were synthesized and characterized. Moreover, their antiviral activities against tobacco mosaic virus were evaluated. The bioassay results indicated that as-prepared compounds showed antiviral activity against tobacco mosaic virus at a concentration of 500?g/mL. The curative activity of compound 4g is 59.5%, which was comparable with positive control (Ningnanmycin, 61.0%). The inactivation activity of the compound 4l exhibited 80.1%, which was higher than that of Ningnanmycin (75.0%), and its protective activity was 88.7%, which is comparable with that of Ningnanmycin (90.7%).