21836-30-6Relevant 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 biological evaluation of novel N-[4-(2-fluorophenoxy)pyridin-2-yl]cyclopropanecarboxamide derivatives as potential c-Met kinase inhibitors
Chen, Ye,Ding, Shi,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Ju,Liu, Yajing,Shi, Jiantao,Wang, Yang,Zhou, Yunpeng
, (2020/03/31)
Three series of novel 4-phenoxypyridine derivatives containing 4-methyl-6-oxo-1,6-dihydropyridazine- 3-carboxamide, 5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide and 4-methyl-3,5-dioxo-2,3,4,5- tetrahydro-1,2,4-triazine-6-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activitives against c-Met kinase and cytotoxic activitives against A549, H460, HT-29 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activitives. The most promising compound 26a (with c-Met IC50 value of 0.016 μM) showed remarkable cytotoxicity against A549, H460, and HT-29 cell lines with IC50 values of 1.59 μM, 0.72 μM and 0.56 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that 4-methyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxamide was more preferred as linker part, and electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activitives. Furthermore, the colony formation, acridine orange/ethidium bromide (AO/EB) staining, apoptosis, and wound-healing assay of 26a were performed on HT-29 and/or A549 cell lines.
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
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.
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.
Aminothienopyridazine inhibitors of tau aggregation: Evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties
Ballatore, Carlo,Crowe, Alex,Piscitelli, Francesco,James, Michael,Lou, Kevin,Rossidivito, Gabrielle,Yao, Yuemang,Trojanowski, John Q.,Lee, Virginia M.-Y.,Brunden, Kurt R.,Smith III, Amos B.
experimental part, p. 4451 - 4461 (2012/08/28)
Previous studies demonstrated that members of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors exhibit a promising combination of in vitro activity as well as favorable pharmacokinetic properties (i.e., brain-penetration and oral bioavailability). Here we report the synthesis and evaluation of several new analogues. These studies indicate that the thienopyridazine core is essential for inhibition of tau fibrillization in vitro, while the choice of the appropriate scaffold decoration is critical to impart desirable ADME-PK properties. Among the active, brain-penetrant ATPZ inhibitors evaluated, 5-amino-N-cyclopropyl-3-(4-fluorophenyl)-4-oxo-3,4- dihydrothieno[3,4-d]pyridazine-1-carboxamide (43) was selected to undergo maximum tolerated dose and one-month tolerability testing in mice. The latter studies revealed that this compound is well-tolerated with no notable side-effects at an oral dose of 50 mg/kg/day.
Synthesis, characterization and antibacterial screening of new pyrazole and pyrazoline-5-one derivatives
Nagaraju,Srinivasulu,Doraswamy,Venkata Ramana
experimental part, p. 293 - 298 (2012/03/11)
A series of N′-(p-toluene sulphonyl)-3-methyl-4-(substituted arylhydrazono)-2-pyrazoline-5-ones and N′-(2-hydroxybenzoyl)-3,5-dimethyl- 4-(substituted arylazo)pyrazoles have been synthesized and characterized by chemical analysis, IR and 1H NMR spectral data. The compounds have been screened for antibacterial activity against Staphylococcus aureus and Escherichia coli.
Synthesis of N′-(2-hydroxybenzoyl)-3-methyl-4-(substituted-phenylhydrazono)-2- pyrazolin-5-ones
Venkata Ramana,Ravindranath
, p. 112 - 113 (2007/10/03)
N′-(2-Hydroxybenzoyl)-3-methyl-4-(substituted-phenylhydrazono)-2- pyrazolin-5-ones have been synthesised by the reaction of 2-(substituted-phenylhydrazono)-ethyl-2,3-dioxobutyrate with salicylic acid hydrazine.
On the Polarographic Reduction Mechanism of Some Heterocyclic Compounds
Malik, Wahid U.,Jain, Rajeev
, p. 191 - 194 (2007/10/02)
For evaluating the mechanistic steps, position at d.m.e. and assigning inner or outer sphere path of electrode processes of a number of pyrazole derivatives, thiazoles and their precursors experiments were carried out in the absence and presence of surfactants.All the compounds gave diffusion-controlled, irreversible waves over the entire pH range (2.0-11.0) studied.In presence of surfactants also, diffusion-controlled but more irreversible waves were obtained.In absence and presence of surfactant (CTAB) values of Kapp and αapp for all these compounds were calculated and have been taken as a proof of inner sphere or outer sphere path of the electrode reaction.Results have been explained on the basis of formation of phenylazo-functionalised surfactant as an intermediate species.
