99068-00-5

Upstream product

• 90-02-8 salicylaldehyde 
• 22214-28-4 4-(2-hydroxyphenyl)but-3-en-2-one 

Downstream Products

• 29026-04-8 1-Methyl-2-o-hydroxyphenylcyclopropan 
• 1310098-50-0 (5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)(o-tolyl)methanone 
• 1310098-51-1 1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-(4-nitrophenyl)ethanone 
• 1310098-49-7 (5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)(p-tolyl)methanone 
• 1310098-52-2 2-chloro-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone 
• 1310098-55-5 2-(3-methyl-1-(phenylsulfonyl)-4,5-dihydro-1H-pyrazol-5-yl)phenol 
• 1310098-56-6 2-(3-methyl-1-tosyl-4,5-dihydro-1H-pyrazol-5-yl)phenol 
• 1310098-48-6 (5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)(phenyl)methanone 
• 1310098-57-7 2-(3-methyl-1-(4-nitrophenylsulfonyl)-4,5-dihydro-1H-pyrazol-5-yl)phenol 
• 1310098-53-3 (2-chlorophenyl) (5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)methanone 
• 1355956-62-5 2-bromo-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone 
• 1376358-68-7 1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-(4-hydroxypiperidin-1-yl)ethanone 
• 1376358-71-2 1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-(2-methylpiperidin-1-yl)ethanone 
• 1376358-73-4 2-(2-ethylpiperidin-1-yl)-1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)ethanone 

Relevant academic research and scientific papers

Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo

It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 μM. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future.

Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors

Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 μM, respectively). The structure–activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 μM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi–Sigma interaction and three Pi–Alkyl interactions.

Tricyclic pyrromonazole [1,5-c][1,3] benzoxazinone derivative as well as preparation method and purpose thereof

The invention discloses a tricyclic pyrromonazole [1,5-c][1,3] benzoxazinone derivative, which has the following structure general formula I shown in the description, wherein R1 is halogen, C1-C6-alkyl or C1-C6-alkoxy; R2 is halogen, C1-C6-alkyl or C1-C6-alkoxy; R3 is halogen, C1-C6-alkyl or C1-C6-alkoxy; R4 is halogen, C1-C6-alkyl or C1-C6-alkoxy. The invention provides a reversible and selectiveBuChE inhibitor; good cholinesterase inhibitory activity is realized; selectivity is realized on the BuChE inhibitory activity, wherein the partial preferred tricyclic pyrromonazole [1,5-c][1,3] benzoxazinone derivative has better BuChE inhibitory activity; the BuChE inhibitory activity of the partial tricyclic pyrromonazole [1,5-c][1,3] benzoxazinone derivative is superior to positive control medicine donepezil.

Identification of human telomerase inhibitors having the core of N-acyl-4,5-dihydropyrazole with anticancer effects

Eight human telomerase inhibitors (5a–5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2?Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50values of 2.06?±?0.17 and 2.89?±?0.62?μM, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50value of 1.86?±?0.51?μM, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA:DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a–8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase.

Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5- tetrahydro-pyrazolo[1,5-d][1,4]oxazepin-8(7H)-one derivatives as telomerase inhibitors

Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4]oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC50 value at 0.78 ± 0.22 μM. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway.

Design and synthesis of novel 5-phenyl-N-piperidine ethanone containing 4,5-dihydropyrazole derivatives as potential antitumor agents

A series of novel 5-phenyl-N-piperidine ethanone-4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassays demonstrated that compounds 4d, 4f, 7a and 7b occupied high antiproliferative activities against SGC-7901, MGC-803 and Bcap-37 cell lines. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 7b showed the most potent inhibitory activity with IC50 value at 2.00 ± 0.40 μM. The active compound 4d was also docked into the telomerase TERT active site to determine the probable binding model. The results indicated that conserved residues Lys189, Asp254 and Gln308 were important for ligand binding via hydrogen bond interactions.

Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents

A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC 50 values of 21.23 ± 0.99, 29.43 ± 0.32 and 30.89 ± 1.07 μM, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC50 value of 4.0 ± 0.32 μM. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model.