68280-85-3Relevant academic research and scientific papers
Synthesis, biological activity, molecular docking studies of a novel series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the acetylcholinesterase inhibitors
Jin, Zhe,Zhang, Chao,Liu, Miao,Jiao, Simeng,Zhao, Jing,Liu, Xiaoping,Lin, Huangquan,Chi-cheong Wan, David,Hu, Chun
, p. 2478 - 2489 (2020/04/27)
The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer’s disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too. HIGHLIGHTS A novel series of 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. The SAR study of the target 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives was summarized. The active sites in the acetylcholinesterase were analyzed by molecular docking technique. Communicated by Ramaswamy H. Sarma.
Synthesis, β-catenin translocation capability and ALP activation activity of 7h-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives
Hou, Shicheng,Xu, Henan,Hu, Jianshu,Hou, Jian,Wang, Yan,Jin, Zhe,Wan, David C. C.,Hu, Chun
, p. 67 - 73 (2018/02/14)
Background: Osteoporosis (OP) is a common bone disease, most often diagnosed in post-menopausal women. The majority of OP treatments are focused on manipulation of the patient's hormone levels, therefore, they are associated with significant adverse effects. Objective: The study aimed to design, synthesize and evaluate the β-Catenin translocation capability and the alkaline phosphatase (ALP) activation activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. Method: The styrene derivatives were synthesized as raw materials, followed by oxidation and condensation reactions, in which 6-aryl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives (1) were obtained. The 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (2) were obtained by a condensation reaction of compound 1 with substituted phenacyl chlorides in acetic acid. The target compounds 3,6-diaryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones (3a-3c) were prepared by compound 2 with substituted alkyl chloride by Williamson reaction. As to 6-benzyl-3-aryl-7H-thiazolo[3,2- b]-1,2,4-triazin-7-one derivatives as the target compounds, the benzaldehyde and acetylglycine used as raw materials, followed by Erlenmeyer-Pl?chl reaction, condensation reaction, hydrolysis reaction, condensation reaction, 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives were obtained, and were converted to the target compounds 6-benzyl-3-(hydroxylaryl)-7Hthiazolo[ 3,2-b]-1,2,4-triazin-7-one derivatives (5a-5d) using reaction with substituted β-phenacyl chlorides. Finally, Williamson reaction were used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]- 1,2,4-triazin-7-ones as target compounds (6a-6e). The β-Catenin translocation capability and the ALP activation activity were tested, and the glycogen synthase kinase-3 (GSK-3) inhibition was simulated by molecular docking. Results: Fourteen 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and characterized by mass spectra, proton NMR and infrared spectra, the β-Catenin translocation capability and the ALP activation activities of the target compounds were tested and calculated. The EC50 value of the ALP activation activity of 6-(4-chlorobenzyl)-3-{4-[(2-dimethylamino)-2- oxoethoxy]phenyl}-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one (6b) was 11.283 μM. The molecular docking results have showed that the target compounds would be GSK-3 inhibitors. Conclusion: Based on the results of the biological activity test, the target compounds have exhibited the β-Catenin translocation capability and the ALP activation activity.
Synthesis and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4-triazin-7- one derivatives as dual binding site acetylcholinesterase inhibitors
Liu, Sijie,Shang, Ruofeng,Shi, Lanxiang,Wan, David Chi-Cheong,Lin, Huangquan
, p. 237 - 244 (2014/06/09)
A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 7a-i were synthesized and evaluated as novel acetylcholinesterase (AChE) inhibitors. All target compounds were evaluated in vitro for the inhibitory activities against AChE via Ellman colorimetric assay. Compound 7c showed an excellent (89.82%) inhibitory activity. The molecular docking studies revealed that 7c, 7d and 7g, with the lateral chain in the para position of the phenyl ring, possessed an optimal docking pose and can perfectly fit into the catalytic active site (CAS) and peripheral anionic site (PAS), simultaneously, and, consequently, exhibited higher inhibitory potency than 7b that bears the same lateral chain as 7g, but in the ortho position of the phenyl ring.
Design, synthesis, and evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7- one derivatives as dual binding site acetylcholinesterase inhibitors
Liu, Sijie,Shang, Ruofeng,Shi, Lanxiang,Zhou, Ran,He, Jingyu,Wan, David Chi-Cheong
, p. 169 - 174 (2014/07/22)
New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as a new drug candidate for the treatment of Alzheimer's disease (AD) through the binding to both catalytic and peripheral sites of the enzyme. Therefore, a se
Asymmetric synthesis of unnatural amino acids and tamsulosin chiral intermediate
Arava, Veera Reddy,Amasa, Srinivasulu Reddy,Goud Bhatthula, Bharat Kumar,Kompella, Laxmi Srinivas,Matta, Venkata Prasad,Subha
supporting information, p. 2892 - 2897 (2013/09/02)
An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.
Design, synthesis, and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4- triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors
Liu, Si-Jie,Cui, Li-Bo,Xu, Hui-Lan,Wang, Tie-Ying,Hu, Chun,Li, Shuo,Lin, Huang-Quan,Wan, David Chicheong
, p. 2607 - 2614 (2014/01/06)
A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors. The target compounds exhibited promising inhibitory activity for AChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by the molecular docking studies.
Design, synthesis, and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4- triazin-7-one derivatives as acetylcholinesterase inhibitors
Liu, Si-Jie,Yang, Liu,Liu, Xiao-Guang,Luo, Ying,Cao, Zi-Jian,Wan, David Chi Cheong,Lin, Huang-Quan,Hu, Chun
scheme or table, p. 5 - 8 (2011/01/03)
The docking study on a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives with acetylcholinesterase has been demonstrated. The synthesis and characterization of a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were described. All target compounds were evaluated in vitro for the inhibitory activities against AChE via Ellman colorimetric assay. Most of the target compounds possessed anti-acetylcholinesterase activity. The preliminary structure-activity relationships were discussed.
