5547-00-2

Upstream product

• 89-25-8 edaravone 
• 100-63-0 phenylhydrazine 
• 110-91-8 morpholine 
• 947-95-5 5-chloro-4-formyl-3-methyl-1-phenyl-1H-pyrazole 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1028090-55-2 (+/-)-2,2,3'-trimethyl-1'-phenyl-1',4',5a',6',8',9'-hexahydrospiro[1,3-dioxane-5,5'-pyrazolo[4',3':5,6]pyrido[2,1-c][1,4]oxazine]-4,6-dione 
• 1028090-57-4 (+/-)-1',3,3'-trimethyl-1-phenyl-1,4,5a,6,8,9-hexahydro-2'H-spiro[pyrazolo[4',3':5,6]pyrido[2,1-c][1,4]oxazine-5,5'-pyrimidine]-2',4',6'(1'H,3'H)-trione 
• 1660146-15-5 3-methyl-1-phenyl-1,4,5a,6,8,9-hexahydro-5H-pyrazolo[4',3':5,6]pyrido[2,1-c][1,4]oxazine-5,5-dicarbonitrile 
• 1082105-74-5 2-(3-methyl-5-morpholino-1-phenyl-1H-pyrazol-4-ylmethylene)malononitrile 

Relevant academic research and scientific papers

Design, synthesis and in-silico & in vitro enzymatic inhibition assays of pyrazole-chalcone derivatives as dual inhibitors of α-amylase & DPP-4 enzyme

A series of pyrazole-chalcone derivatives were designed, synthesized and evaluated for their in vitro α-amylase & DPP-4 inhibitory activity. The structure of the compounds thus prepared was confirmed by analytical, and spectral techniques, 1H-NMR, 13C-NMR and Mass spectroscopy. To preliminarily investigate the molecular targets and to confirm the experimental activity testing for these anti-diabetic compounds, the molecular docking studies were determined, using different target receptors i.e., DPP-4 (PDB: 2OLE), PPARγ (PDB: 5Y2O) & α-amylase enzyme (PDB: 5E0F). The docking study results revealed that pyrazole-chalcone derivatives exhibited better binding interaction to α-amylase enzyme over the DPP-4 enzyme & PPARγ. Depending on in silico experiments the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to enzyme-based in vitro α-amylase, DPP-4 inhibitory, and antioxidant activity. ADMET parameters like HBD, HBA, PSA, cLogP, molecular weight, bioavailability, and drug-likeness further confirmed that the compounds are potential lead compounds for future study. Compounds 4d and 6a exhibited highest activity toward α-amylase enzyme and DPP-4 enzyme.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as sphingosine kinase 1 inhibitor

Sphingosine kinase 1 (SphK1) has emerged as an attractive drug target for different diseases. Recently, discovered SphK1 inhibitors have been recommended in cancer therapeutics; however, selectivity and potency are great challenges. In this study, a novel series of benzimidazoles was synthesized and evaluated as SphK1 inhibitors. Our design strategy is twofold: It aimed first to study the effect of replacing the 5-position of the benzimidazole ring with a polar carboxylic acid group on the SphK1-inhibitory activity and cytotoxicity. Our second aim was to optimize the structures of the benzimidazoles through the elongation of the chain. The enzyme inhibition potentials against all the synthesized compounds toward SphK1 were evaluated, and the results revealed that most of the studied compounds inhibited SphK1 effectively. The binding affinity of the benzimidazole derivatives toward SphK1 was measured by fluorescence binding and molecular docking. Compounds 33, 37, 39, 41, 42, 43, and 45 showed an appreciable binding affinity. Therefore, the SphK1-inhibitory potentials of compounds 33, 37, 39, 41, 42, 43, and 45 were studied and IC50 values were determined, to reveal high potency. The study showed that these compounds inhibited SphK1 with effective IC50 values. Among the studied compounds, compound 41 was the most effective one with the lowest IC50 value and a high cytotoxicity on a wide spectrum of cell lines. Molecular docking revealed that most of these compounds fit well into the ATP-binding site of SphK1 and form hydrogen bond interactions with catalytically important residues. Overall, the findings suggest the therapeutic potential of benzimidazoles in the clinical management of SphK1-associated diseases.

Design and synthesis of new pyrazolylbenzimidazoles as sphingosine kinase-1 inhibitors

Sphingosine-1 kinase (SphK1) is one of the important enzymes of phospholipids and its inhibition is one of the therapeutic strategies for different diseases. SphK1 over expression is observed in different types of cancer indicating its important role in tumor growth. In search of effective SphK1 inhibitors, a new series of pyrazolylbenzimidazoles was synthesized and evaluated as sphingosine kinase-1 (SphK1) inhibitors. In order to evaluate the binding affinities of all the synthesized compounds, all compounds were subjected to docking analysis and fluorescence quenching. The results indicated that there is a consistency between the docking and the fluorescence quenching results, which revealed that compounds 47 and 48 exhibited significant decrease in the fluorescence intensity of SphK1 as well as they formed stable protein–ligand complexes. In addition, enzyme inhibition assay was performed which showed effective inhibitory potential toward SphK1. Moreover, IC50 values displayed that compounds 47 and 48 were the most promising compounds. In addition, antiproliferation study for all the synthesized compounds was performed against NCI-60 cell line panel. The target compounds 47 and 48 demonstrated effective antitumor activity and growth inhibitory potential toward cancer cell lines. Most of these compounds fit well into the ATP-binding site of SphK1 and form significant hydrogen-bonding interactions with catalytically relevant residues as predicted by molecular docking. In this article, insight has been given for the importance of pyrazolylbenzimidazoles as SphK1 inhibitors and the perspectives that they hold for future research. [Figure not available: see fulltext.]

Synthesis of some novel pyrazolopyridooxazine, pyrazoloquinolizines, pyrazoloindolizine and pyrazolopyranopyrimidinone derivatives

Different pyrazolone derivatives were prepared as starting materials for the synthesis of pyrazolopyridooxazine, pyrazoloquinolizines, pyrazoloindolizine, 1,4-oxazinopyrazolines and pyrazolopyranopyrimidinone derivatives via reactions with different reagents applying the one pot multicomponent reaction using microwave and ultrasound irradiation in some cases.

Design, synthesis and molecular docking study of novel quinoxalin-2(1H)-ones as anti-tumor active agents with inhibition of tyrosine kinase receptor and studying their cyclooxygenase-2 activity

On continuation to our work, new quinoxalin-2(1H)-ones were synthesized to study their cytotoxic effect against HepG-2 and MCF-7 with their effect on the human tyrosine kinase (TRK). Compounds 12, 18, 15, 13, 11a, 20 and 16, respectively, were found to be more potent than cisplatin against HepG2 and selective to TRK. Also, compounds 12, 18, 20, 13, 14, and 22, respectively, exhibited decidedly activity against MCF- 7 and selectivity against human TRK compared to cisplatin. A molecular docking study was also performed to gain comprehensive understanding into plausible binding modes and to conclude the structure activity relationships of the synthesized compounds. Moreover, anti-inflammatory activity was studied. Compounds 12, 15, 18 and 22 were found to be potent and selective against COX-2.

Scope and limitations of the T-reaction employing some functionalized C-H-acids and naturally occurring secondary amines

Scope and limitations of the T-reaction with emphasis on using chiral, natural products as starting materials to prepare novel chiral heterocycles is studied and the diastereoselective introduction of newly formed stereocenters is explained via proposed mechanisms.

Introduction of N-containing heterocycles into pyrazole by nucleophilic aromatic substitution

The nucleophilic aromatic substitution on 5-chloropyrazoles activated by the electron-withdrawing formyl group offers a useful method to introduce a wide range of N-containing heterocycles into them. The rate of reaction was greatly affected by the electronic nature of the N-1 substitution.