35523-67-2Relevant academic research and scientific papers
Synthesis of 5-Methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one in Supercritical Carbon Dioxide
Baklykov,Rusinov,Rusinov,Charushin,Kopchuk,Zyryanov,Artem’ev
, (2019)
5-Methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one, an intermediate product in the synthesis of the antiviral drug Triazid, was obtained for the first time by condensation of 3H-1,2,4-triazol-5-amine with ethyl acetoacetate in the presence of a catalytic a
6-Nitrotriazolo[1,5-a]pyrimidines as promising structures for pharmacotherapy of septic conditions
Savateev,Ulomsky,Fedotov,Rusinov,Sivak,Lyubishin,Kuzmich,Aleksandrov
, p. 421 - 428 (2017)
Promising 6-nitro-1,2,4-triazolo[1,5-a]pyrimidine analogues, structural analogues of synthetic inhibitors of adenosine receptors, were sorted out on the basis of quantum-chemical calculations. The compounds were synthesized by nitration and chlorodeoxygenation reactions. The in vivo activity of 6-nitroheterocycles was studied and the affinity to adenosine receptor A2A was demonstrated in regard to septic conditions.
Comparative study between the anti-P. falciparum activity of triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives and the identification of new PfDHODH inhibitors
Silveira, Flávia F.,de Souza, Juliana O.,Hoelz, Lucas V.B.,Campos, Vinícius R.,Jabor, Valquíria A.P.,Aguiar, Anna C.C.,Nonato, M. Cristina,Albuquerque, Magaly G.,Guido, Rafael V.C.,Boechat, Nubia,Pinheiro, Luiz C.S.
, (2020/11/10)
In this work, we designed and synthesized 35 new triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives as P. falciparum inhibitors (3D7 strain). Thirty compounds exhibited anti-P. falciparum activity, with IC50 values ranging from 0.030 to 9.1 μM. The [1,2,4]triazolo[1,5-a]pyrimidine derivatives were more potent than the pyrazolo[1,5-a]pyrimidine and quinoline analogues. Compounds 20, 21, 23 and 24 were the most potent inhibitors, with IC50 values in the range of 0.030–0.086 μM and were equipotent to chloroquine. In addition, the compounds were selective, showing no cytotoxic activity against the human hepatoma cell line HepG2. All [1,2,4]triazolo[1,5-a]pyrimidine derivatives inhibited PfDHODH activity in the low micromolar to low nanomolar range (IC50 values of 0.08–1.3 μM) and did not show significant inhibition against the HsDHODH homologue (0–30% at 50 μM). Molecular docking studies indicated the binding mode of [1,2,4]triazolo[1,5-a]pyrimidine derivatives to PfDHODH, and the highest interaction affinities for the PfDHODH enzyme were in agreement with the in vitro experimental evaluation. Thus, the most active compounds against P. falciparum parasites 20 (R = CF3, R1 = F; IC50 = 0.086 μM), 21 (R = CF3; R1 = CH3; IC50 = 0.032 μM), 23, (R = CF3, R1 = CF3; IC50 = 0.030 μM) and 24 (R = CF3, 2-naphthyl; IC50 = 0.050 μM) and the most active inhibitor against PfDHODH 19 (R = CF3, R1 = Cl; IC50 = 0.08 μM - PfDHODH) stood out as new lead compounds for antimalarial drug discovery. Their potent in vitro activity against P. falciparum and the selective inhibition of the PfDHODH enzyme strongly suggest that this is the mechanism of action underlying this series of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives.
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
supporting information, (2021/07/25)
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.
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.
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
supporting information, p. 349 - 352 (2019/08/30)
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.
Discovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway
Wang, Shuai,Ma, Xu-Bin,Yuan, Xiao-Han,Yu, Bin,Xu, Yi-Chao,Liu, Hong-Min
, (2020/07/21)
Mitochondria are known as “powerhouse of cells” and play the role of a bridge in redox balance, cell apoptosis, and autophagy. ROS accumulation can cause mitochondria damage, while the injured mitochondria will further enhance ROS levels reciprocally. Herein, we synthesized a novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compounds 4a-4v and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds 4o and 4p inhibited gastric cancer cells at micromolar level. Compound 4o caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound 4o against gastric cancer cell. To our surprising, ROS level was increased by compound 4o and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound 4o in MGC-803 cells. Taken together, compound 4o exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound 4o may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.
Applications of alkaloid essramycin and derivative thereof in resisting of plant viruses
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Paragraph 0051-0056, (2020/01/30)
The invention relates to applications of alkaloid essramycin and a derivative thereof in resisting of plant viruses, wherein the chemical structural formula of the alkaloid essramycin is represented in the specification, specifically the alkaloid essramyc
Discovery, Structural Optimization, and Mode of Action of Essramycin Alkaloid and Its Derivatives as Anti-Tobacco Mosaic Virus and Anti-Phytopathogenic Fungus Agents
Wang, Tienan,Yang, Shan,Li, Hongyan,Lu, Aidang,Wang, Ziwen,Yao, Yingwu,Wang, Qingmin
, p. 471 - 484 (2020/02/18)
Plant diseases seriously affect crop yield and quality and are difficult to control. Marine natural products (MNPs) have become an important source of drug candidates with new biological mechanisms. Marine natural product essramycin (1) was found to have
Discovery of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new bromodomain-containing protein 4 (BRD4) inhibitors
Wang, Shuai,Shen, Dandan,Zhao, Lijie,Yuan, Xiaohan,Cheng, Jialing,Yu, Bin,Zheng, Yichao,Liu, Hongmin
supporting information, p. 418 - 422 (2019/09/03)
Targeting bromodomain-containing protein 4 (BRD4) has been proved to be an effective strategy for cancer therapy. To date, numerous BRD4 inhibitors and degraders have been identified, some of which have advanced into clinical trials. In this work, a focused library of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives were discovered to be able to inhibit BRD4. WS-722 inactivated BRD4 (BD1/BD2), BRD2 (BD1/BD2) and BRD3 (BD1/BD2) broadly with the IC50 values less than 5 μmol/L. Besides, WS-722 inhibited growth of THP-1 cells with an IC50 value of 3.86 μmol/L. Like (+)-JQ1, WS-722 inhibited BRD4 in a reversible manner and enhanced protein stability. Docking studies showed that WS-722 occupied the central acetyl-lysine (Kac) binding cavity and formed a hydrogen bond with Asn140. In THP-1 cells, WS-722 showed target engagement to BRD4. Cellular effects of WS-722 on THP-1 cells were also examined, showing that WS-722 could block c-MYC expression, induce G0/G1 phase arrest and p21 up-regulation, and promote differentiation of THP-1 cells. BRD4 inhibition by WS-722 resulted in cell apoptosis and up-regulated expression of cleaved caspased-3/7 and PARP in THP-1 cell lines. The [1,2,4]triazolo[1,5-a]pyrimidine is a new template for the development of new BRD4 inhibitors.
