5469-45-4Relevant articles and documents
2H-thiazolo [3, 2-b]-1, 2, 4-triazine-3, 7-diketone derivative and application thereof
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, (2020/12/29)
The invention discloses a 2Hthiazolo [3, 2b] 1, 2, 4triazine 3, 7diketone derivative as shown in a general formula I or pharmaceutically acceptable hydrate and salt thereof, the 2Hthiazolo [3, 2b] 1,2, 4triazine 3, 7diketone derivative comprises stereoisomers or tautomers thereof, and R1 and R2 in the general formula I can be optionally selected from one, two or three independently selected fromhydrogen, alkyl, alkoxy, halogen, hydroxyl, acetyl, propionyl, nitro or trifluoromethyl. The 1, 2, 4-triazine 3, 7diketone derivative has an obvious inhibiting effect on acetylcholin esterase, and isused for enhancing the memory of a patient suffering from dementia and Alzheimer's disease. The invention also relates to a preparation method of the compound and the application of the compound in preparation of drugs for treating Alzheimer's disease.
Biocatalytic retrosynthesis approaches to d-(2,4,5-trifluorophenyl)alanine, key precursor of the antidiabetic sitagliptin
Parmeggiani, Fabio,Rué Casamajo, Arnau,Colombo, Danilo,Ghezzi, Maria Chiara,Galman, James L.,Chica, Roberto A.,Brenna, Elisabetta,Turner, Nicholas J.
, p. 4368 - 4379 (2019/08/21)
The integration of biocatalytic steps in retrosynthetic analysis of a target molecule offers multiple advantages, such as reduction of the environmental footprint of the process, viability of milder and safer reaction conditions, and accessibility of transformations that are challenging with traditional chemical synthesis. Herein, six chemo-enzymatic routes are described for the synthesis of a fluorinated d-phenylalanine derivative, precursor of the blockbuster antidiabetic drug sitagliptin. All routes start from the same aldehyde precursor and involve at least one biocatalytic step, including reductive amination, transamination, deracemisation, hydroamination, and alkene reduction. The target molecule was obtained in 2-5 steps from the aldehyde, with ee up to >99% and in 36-62% isolated yield. Furthermore, as part of one of the routes, the first example of a fully biocatalytic conversion of a cinnamic acid derivative to the corresponding d-phenylalanine (formal d-selective hydroamination) is reported.
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.
