24415-66-5Relevant articles and documents
Br?nsted acid-promoted ‘on–water’ C(sp3)-H functionalization for the synthesis of isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the SKP2-CKS1 interaction
Yuan, Shuo,Wang, Sixi,Zhao, Min,Zhang, Danqing,Chen, Jinjie,Li, Jian-Xin,Zhang, Jingya,Song, Yihui,Wang, Jinyi,Yu, Bin,Liu, Hongmin
, p. 349 - 352 (2020)
The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules, which have showed broad and interesting biological activities. The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community. In this communication, we report an efficient Br?nsted acid-promoted C(sp3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine, 2-formylbenzoic acid and various anilines. The title compounds were generated in high to excellent yields (up to 96%) regardless of the electronic nature and steric effects of the substituents. In this reaction, an isoindolinone scaffold, one C[sbnd]C single bond, and two C[sbnd]N bonds were formed simultaneously with high atom economy. In this work, we have envisioned that the methyl group linked to the electron-deficient N-heterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry. Besides, the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.
Design and synthesis of new indole containing biaryl derivatives as potent antiproliferative agents
Yuan, Shuo,Feng, Si-Qi,Li, An-Qi,Zuo, Jia-Hui,Zhang, Dan-Qing,Xing, Yu-Jie,Xie, Zhiyu,Yu, Bin,Liu, Hong-Min
, (2021)
A new series of indole containing biaryl derivatives were designed and synthesized, and further biological evaluations of their antiproliferative activity against cancer cell lines (MGC-803 and TE-1 cells) were also conducted. Of these synthesized biaryls, compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) performed as the most potent antiproliferative agent that inhibited cell viability of MGC-803 cells with an IC50 value of 8.28 μM. In addition, investigation of mechanism exhibited that the compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) could inhibit the expression of c-Myc and glycolysis related proteins, decrease the ATP and lactate production, and further induce apoptosis by activating the AMP-activated protein kinase (AMPK) and p53 signaling pathways.
An Unequivocal Synthesis of Some Substituted 1,2,4-TriazoloPyrimidines
Stanovnik, Branko,Urleb, Uros,Tisler, Miha
, p. 601 - 606 (1987)
An unequivocal synthesis of 5-chloro-7-methyl- (8) and 7-methyl-1,2,4-triazolopyrimidine (10) from 2-amino-4-chloro-6-methylpyrimidine (5) through the corresponding amidine 6 and formamide oxime 7 was developed.It was unambigously shown by comparison of the chemical shifts and the magnitude of coupling constants that the compounds obtained by condensation of 3-amino-1,2,4-triazole (12) and ethyl acetoacetate (13) and some further transformations are isomeric 5-methyl substituted 1,2,4-triazolopyrimidines 1, 9, and 11. - Keywords: 1,2,4-Triazolopyrimidines; Cyclization with N-N bond formation; Structure determination by NMR
ISOTOPICALLY-LABELLED TRAPIDIL DERIVATIVES
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Paragraph 00177; 00178, (2021/10/02)
Provided are isotopically-labelled Trapidil derivatives useful for the treatment of Parkinson's disease and movement disorders associated with Parkinson's disease. The isotopically-labelled Trapidil derivatives include deuterated Trapidil derivatives. Additionally provided are combination therapies of isotopically-labelled Trapidil derivatives and additional therapeutic agents for the treatment of Parkinson's disease and movement disorders associated with Parkinson's disease.
Discovery of the Triazolo[1,5- a]Pyrimidine-Based Derivative WS-898 as a Highly Efficacious and Orally Bioavailable ABCB1 Inhibitor Capable of Overcoming Multidrug Resistance
Wang, Shuai,Wang, Sai-Qi,Teng, Qiu-Xu,Lei, Zi-Ning,Chen, Zhe-Sheng,Chen, Xiao-Bing,Liu, Hong-Min,Yu, Bin
, p. 16187 - 16204 (2021/11/18)
Targeting P-glycoprotein (ABCB1 or P-gp) has been recognized as a promising strategy to overcome multidrug resistance. Here, we reported our medicinal chemistry efforts that led to the discovery of the triazolo[1,5-a]pyrimidine derivative WS-898 as a highly effective ABCB1 inhibitor capable of reversing paclitaxel (PTX) resistance in drug-resistant SW620/Ad300, KB-C2, and HEK293/ABCB1 cells (IC50 = 5.0, 3.67, and 3.68 nM, respectively), more potent than verapamil and zosuquidar. WS-898 inhibited the efflux function of ABCB1, thus leading to decreased efflux and increased intracellular PTX concentration in SW620/Ad300 cells. The cellular thermal shift assay indicated direct engagement of WS-898 to ABCB1. Furthermore, WS-898 stimulated the ATPase activity of ABCB1 but had minimal effects on cytochrome P450 3A4 (CYP3A4). Importantly, WS-898 increased PTX sensitization in vivo without obvious toxicity. The results suggest that WS-898 is a highly effective triazolo[1,5-a]pyrimidine-based ABCB1 inhibitor and shows promise in reversing ABCB1-mediated PTX resistance.
