40469-00-9Relevant academic research and scientific papers
Tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one scaffold derivatives: Synthesis and biological evaluation as selective BuChE inhibitors
Chen, Shi-Chao,Qiu, Guo-Liang,Li, Bo,Shi, Jing-Bo,Liu, Xin-Hua,Tang, Wen-Jian
, p. 194 - 204 (2018/02/14)
BuChE inhibitors play important roles in treatment of patients with advanced Alzheimer's disease (AD). A series of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one derivatives were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylch
Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors
Qiu, Guo-Liang,He, Shao-Sheng,Chen, Shi-Chao,Li, Bo,Wu, Hui-Hui,Zhang, Jing,Tang, Wen-Jian
, p. 1506 - 1515 (2018/10/15)
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.
Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo
Wang, Yang,Cheng, Fei Xiong,Yuan, Xiao Long,Tang, Wen Jian,Shi, Jing Bo,Liao, Chen Zhong,Liu, Xin Hua
, p. 231 - 251 (2016/05/02)
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.
Identification of human telomerase inhibitors having the core of N-acyl-4,5-dihydropyrazole with anticancer effects
Xiao, Xuan,Ni, Yong,Jia, Ying-Ming,Zheng, Min,Xu, Han-Fei,Xu, Jun,Liao, Chenzhong
, p. 1508 - 1511 (2016/07/27)
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.
Novel 4-bromo-2-(3-methyl-1-(substituted-phenylsulfonyl)-4,5-dihydro-1-H- pyrazol-5-yl)phenol derivatives: Synthesis and antibacterial activity
Cheng, Qing,Jia, Ying-Ming,Cheng, Fei-Hu,Liu, Xin-Hua
, p. 572 - 577 (2014/05/20)
A series of novel 4-bromo-2-(3-methyl-1-(substituted-phenylsulfonyl)-4,5- dihydro-1H-pyrazol-5-yl) phenol derivatives were synthesized and characterized by NMR, ESI-MS. Compound 3c was determined by X-ray. Biological activity tests results show that compound 3h displayed activity with MIC of 0.39, 0.78, 1.562 μg/mL against B. subtilis ATCC 6633, S. aureus ATCC 6538, P. fluorescens ATCC 13525 and could strongly inhibit S. aureus DNA gyrase and B. subtilis DNA gyrase with IC50s of 0.25 and 0.18 μg/mL respectively.
POLYMETHINE DYES BASED ON BENZOPYRYLIUM IONS
Makin, S. M.,Markina, T. A.,Boiko, I. I.
, p. 2182 - 2187 (2007/10/02)
A method is described for the synthesis of a series of benzopyrylium polymethine dyes by the acid cyclization of 2-hydroxystyryl polyenyl ketones, obtained by the successive crotonic condensation of aliphatic or alicyclic ketones initially with salicylaldehyde and its alkyl or halogen derivatives and then with aromatic aldehydes containing a p-methoxyphenyl or 9-alkylcarbazole fragment.The electronic absorption spectra of the new benzopyrylium dyes were studied.
