18804-77-8Relevant academic research and scientific papers
Synthesis of arylhydrazone-based molecular switches using aryldiazonium silica sulfate nanocomposites and analysis of their isomerization
Abbaspourrad, Alireza,Aghaei, Hamidreza,Chermahini, Alireza Najafi,Khazdooz, Leila,Soltani, Solmaz,Zarei, Amin
, (2021/06/26)
A fast and efficient method for the synthesis of a series of arylhydrazones by reacting aryldiazonium silica sulfate nanocomposites with malononitrile, ethyl acetoacetate and dimedone is reported. All reactions were carried out in water at room temperature and the corresponding products were obtained in 77–87% yields. The existence of two kinds of intramolecular hydrogen bonds in the arylhydrazones synthesized using ethyl acetoacetate enables these compounds to be switched by rotation about the hydrazone C[dbnd]N bond, which leads to a reversible isomerization between their E and Z configurations. This switching can be controlled by changing the polarity of the solvents. The E/Z ratio of each synthesized compound was studied in CHCl3 and DMSO. The ratios of the E/Z were calculated using 1H NMR data in both CDCl3 and DMSO?d6, and used to calculate ΔG° for the E-Z isomerization of each synthesized compound in these two solvents. By changing the solvent from CHCl3 to DMSO, the E/Z ratios decreased. The results demonstrated that the ΔG° values for the formation of Z isomers were more negative than those of the E isomers in DMSO. This is why Z isomers are more stable than E isomers in DMSO. The results of density functional theory (DFT) calculations at B3LYP/6–311++G (d,p) level of theory, were in agreement with the experiments and confirmed the increased stability of Z isomers in DMSO. In most cases, DFT calculation in CDCl3 and DMSO indicate that the dipole moments of the Z isomers are significantly higher than those of the E isomers. Finally, the effect of temperature on the E-Z isomerization was studied using dynamic 1H NMR. The findings demonstrated that temperature does not have any significant effect on the E-Z isomerization in CDCl3 and DMSO?d6.
Design, synthesis and anti-tumor evaluation of 1,2,4-triazol-3-one derivatives and pyridazinone derivatives as novel CXCR2 antagonists
Chu, Bizhu,Jiang, Yuyang,Li, Qinyuan,Liu, Zijian,Luo, Jingyi,Shi, Zhichao,Xin, Qilei,Ye, Lizhen,Zhan, Feng,Zhang, Xun,Zhu, Qingyun
, (2021/09/20)
Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid–leucine–arginine sequence-contained chemokines CXCs (ELR+ CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block
Novel potent bifunctional carboxylesterase inhibitors based on a polyfluoroalkyl-2-imino-1,3-dione scaffold
Makhaeva, Galina F.,Lushchekina, Sofya V.,Boltneva, Natalia P.,Serebryakova, Olga G.,Kovaleva, Nadezhda V.,Rudakova, Elena V.,Elkina, Natalia A.,Shchegolkov, Evgeny V.,Burgart, Yanina V.,Stupina, Tatyana S.,Terentiev, Alexey A.,Radchenko, Eugene V.,Palyulin, Vladimir A.,Saloutin, Victor I.,Bachurin, Sergey O.,Richardson, Rudy J.
, (2021/04/15)
An expanded series of alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates (HOPs) 3 was obtained via Cu(OAc)2-catalyzed azo coupling. All were nanomolar inhibitors of carboxylesterase (CES), while moderate or weak inhibitors of acetylcholinesterase and butyrylcholinesterase. Steady-state kinetics studies showed that HOPs 3 are mixed type inhibitors of the three esterases. Molecular docking studies demonstrated that two functional groups in the structure of HOPs, trifluoromethyl ketone (TFK) and ester groups, bind to the CES active site suggesting subsequent reactions: formation of a tetrahedral adduct, and a slow hydrolysis reaction. The results of molecular modeling allowed us to explain some structure-activity relationships of CES inhibition by HOPs 3: their selectivity toward CES in comparison with cholinesterases and the high selectivity of pentafluoroethyl-substituted HOP 3p to hCES1 compared to hCES2. All compounds were predicted to have good intestinal absorption and blood-brain barrier permeability, low cardiac toxicity, good lipophilicity and aqueous solubility, and reasonable overall drug-likeness. HOPs with a TFK group and electron-donor substituents in the arylhydrazone moiety were potent antioxidants. All compounds possessed low cytotoxicity and low acute toxicity. Overall, a new promising type of bifunctional CES inhibitors has been found that are able to interact with the active site of the enzyme with the participation of two functional groups. The results indicate that HOPs have the potential to be good candidates as human CES inhibitors for biomedicinal applications.
Design, synthesis and biological evaluation of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment
Duan, Yongli,Tang, Qidong,Xiong, Hehua,Zhang, Han,Zhang, Jianqing,Zhang, Qian,Zheng, Pengwu
, (2020/03/23)
A series of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment were designed, synthesized, and evaluated for their biological activity. Most compounds showed effective inhibitory activity against cancer cell lines of A
Synthesis and bioevaluation study of novel N-methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors
Wang, Linxiao,Xu, Shan,Chen, Xiuying,Liu, Xiaobo,Duan, Yongli,Kong, Dejia,Zhao, Dandan,Zheng, Pengwu,Tang, Qidong,Zhu, Wufu
, p. 245 - 256 (2017/12/06)
Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were
Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinase inhibitors
Wang, Lin Xiao,Liu, Xiaobo,Xu, Shan,Tang, Qidong,Duan, Yongli,Xiao, Zhen,Zhi, Jia,Jiang, Liwen,Zheng, Pengwu,Zhu, Wufu
, p. 538 - 551 (2017/11/01)
In continue to our previous research, eight series of pyrrolo[2,3-b]pyridine and pyrrolo[2,3-d]pyrimidine derivatives bearing pyridazinone moiety were designed, synthesized, and the in vitro antitumor activity was evaluated against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). Some selected compounds (22f, 22g, 26c and 26e) were evaluated for the activity against c-Met kinase, and according to the results of kinase inhibitory activity, the compound 22g was further evaluated for other four tyrosine kinases (Flt-3, VEGFR-2, c-Kit and EGFR) to test the enzyme-based selectivity. The most promising compound 22g showed excellent activity than lead compound Foretinib against A549, HepG2, MCF-7 and PC-3 cell lines, with the IC50 values of 2.19 ± 0.45 μM, 1.32 ± 0.26 μM, 6.27 ± 1.04 μM and 4.63 ± 0.83 μM. The structure–activity relationships (SARs) and docking studies indicated that the pyrrolo[2,3-b]pyridine derivatives bearing 4-oxo-pyridazinone moiety was superior to the pyrrolo[2,3-d]pyrimidine derivatives bearing 6-oxo-pyridazinone moiety. What's more, the target compounds modified with X and Y (X = H, Y = H) were favorable to the activity. And electron drawing groups (EWGs) of 4-Cl-3CF3 on the aryl group show the best activity.
Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and related derivatives
Maggio, Benedetta,Raffa, Demetrio,Raimondi, Maria Valeria,Cascioferro, Stella,Plescia, Fabiana,Schillaci, Domenico,Cusimano, Maria Grazia,Leonchiks, Ainars,Zhulenkovs, Dmitrijs,Basile, Livia,Daidone, Giuseppe
, (2016/04/20)
A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 μM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 μM.
Synthesis and antibacterial activity of some novel 4-aryl hydrazono-2,5-disubstituted-2,4-dihydro-3H-pyrazol-3-ones
Singh, Vipin Kumar
, p. 429 - 432 (2019/01/21)
4-Aryl hydrazono-2,4-dihydro-3H-pyrazol-2,5-disubstituted-3-ones were prepared by the reaction of ethyl-2-arylhydrazono-3-oxybutyrates with substituted hydrazines in the presence of glacial acetic acid at reflux temp. The synthesized compounds have been c
Mechanically activated solid-state synthesis of phenylhydrazone derivatives via high-speed ball milling
Zhu, Xingyi,Chen, Yuanyuan,Chen, Yuhe,Wang, Jue,Su, Weike
, p. 621 - 626 (2014/07/21)
A series of phenylhydrazone derivatives was synthesized from arenediazonium tetrafluoroborates and active methylene compounds under high-speed ball milling. The reaction occurred in the absence of the solvent and products were obtained in good yield within short reaction times (no more than 30 min).
Synthesis and antimicrobial activity of pyrazolinones and pyrazoles having benzothiazole moiety
Amir, Mohd.,Javed, Sadique A.,Hassan, Mohd. Zaheen
experimental part, p. 1261 - 1270 (2012/07/31)
A new class of 4-arylhydrazono-1-benzothiazolyl-3-methylpyrazolin-5-ones (3a-j) and 4-arylazo-1-benzothiazolyl-3,5-dimethylpyrazoles (4a-j) were designed as pharmacophore hybrids between pyrazolinone/pyrazole and benzothiazole moiety. The target molecules were efficiently synthesized by the cyclization of various oxobutyrates/pentane-2,4-dione derivatives with 6-chloro-2- hydrazinobenzothiazole in the presence of glacial acetic acid. The compounds were evaluated for their in vitro antimicrobial activity. Preliminary study of the structure-activity relationship revealed that electron-withdrawing groups in phenyl ring had a promising effect on the antimicrobial activity. Also, correlation study has been used to establish the relationships between the antibacterial activity and physicochemical parameter clogP. Springer Science+Business Media, LLC 2011.
