1973-04-2Relevant academic research and scientific papers
SARs of a novel series of s-triazine compounds targeting vimentin to induce methuotic phenotype
Zhang, Lei,Qu, Zhipeng,Wu, Jianping,Yao, Shining,Zhang, Qingqing,Zhang, Tao,Mo, Lian,Yao, Qizheng,Xu, Ying,Chen, Ruihuan
, (2021/02/09)
Herein, we describe the design, synthesis and structure?activity relationships of a series of novel s-triazine compounds can induce methuotic phenotype in various types of cancer cells. (E)-1-(4-Chlorophenyl)-3-(4-((4-morpholino-6-styryl-1,3,5-triazine-2-yl)amino)phenyl)urea, compound V6, exhibited a striking methuotic phenotype with a minimal effective concentration of less than 10 nM in U87 glioblastoma cells. Based on structure?activity relationship studies, we designed and synthesized an active probe P1 that retained the full potential of V6 in inducing the methuotic phenotype in U87 glioblastoma cells. Using this probe following affinity-based proteomic profiling strategy, we identified vimentin as the specific target protein of compound V6. Molecular docking revealed that V6 can form hydrogen bonds with vimentin at 273R and 276Y in its rod domain.
N-methyltriazine synthesis method
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Paragraph 0021-0024; 0029-0032; 0037-0040; 0045-0048, (2021/04/26)
The invention discloses an N-methyltriazine synthesis method, which comprises the following steps of S1, dissolving cyanogen chloride and acetonitrile in a solvent, adding a catalyst and hydrogen chloride, and carrying out a reaction to obtain 2-methyl-4, 6-dichloro-1, 3, 5-s-triazine, S2, enabling 2-methyl-4, 6-dichloro-1, 3, 5-s-triazine to react with sodium methoxide to obtain 2-methyl-4-methoxy-6-chloro-1, 3, 5-s-triazine, and S3, carrying out condensation reaction on the 2-methyl-4-methoxy-6-chloro-1, 3, 5-s-triazine and methylamine to obtain the N-methyl triazine. The invention provides a novel reaction route for synthesizing N-methyltriazine, the cost of used raw materials is low, the yield of synthesized N-methyltriazine is high and reaches 96% or above, potential safety hazards caused by chlorine and Grignard reagents used in a traditional synthesis method are avoided, and industrial production is facilitated.
Synthesis method of dihalogenated s-triazine
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Paragraph 0032-0035, (2021/04/14)
The invention discloses a synthesis method of dihalogenated s-triazine. The method comprises the following steps: dissolving a substituted nitrile compound and a halogenated nitrile compound in a certain solvent, adding a certain catalyst, and introducing halogenated hydrogen at a certain temperature for a certain period of time, and reacting to obtain the dihalogenated s-triazine. The invention provides a new reaction route for synthesizing the dihalogenated s-triazine, the dihalogenated s-triazine is prepared by taking the substituted nitrile compound and the halogenated nitrile compound as raw materials and adopting a one-step reaction, the reaction steps and process are saved, the process is simple and convenient, the cost is low, the product yield is high and reaches 99 percent or above, and moreover, a dangerous process of Grignard reaction is avoided in the synthesis process, the production risk is reduced, and meanwhile, the problem of environmental pollution is avoided.
Trizaine-based dehydrative condensation reagents bearing carbon-substituents
Kitamura, Masanori,Komine, Sayaka,Kunishima, Munetaka,Yamada, Kohei
, (2020/02/22)
Herein, we report on the synthesis of alkyl-, aryl-, and alkynyl-substituted chlorotriazines and their ammonium salts, and demonstrate their utility in dehydrative condensation reactions. Although the electrophilicity of these reagents is mainly dependent on the hybridization of the carbon-substituents, it was found that bulky 2,6-dimethylphenyl group-substituted reagents resulted in the highest product yields because of a slight increase in reagent electrophilicity and/or steric hindrance favorable for desired dehydrative condensation reactions.
NOVEL 2,4,6-TRISUBSTITUTED S-TRIAZINE COMPOUND, PREPARATION METHOD THEREFOR, AND USE THEREOF
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Paragraph 0069, (2019/04/05)
The present invention provides a 2,4,6-trisubstituted s-triazine compound represented by general formula (I) or pharmaceutically acceptable salts, prodrugs or solvates thereof, a preparation method therefor, and use of these compounds in preparing drugs for preventing or treating diseases associated with protein kinase and vimentin dysregulation, and cell vacuolization, and in particular, drugs for treating or preventing cancer growth and metastasis, tissue fibrosis and atherosclerosis.
NITROGEN HEXACYCLE COMPOUNDS AS INHIBITORS OF p97 COMPLEX
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Paragraph 2103-2104, (2016/12/22)
Nitrogen hexacycle compounds having an arylalkyl amine substituent at the P4 position and a substituted 5:6 bicyclic group at the P2 position of the nitrogen hexacycle as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the nitrogen hexacycle, the aryl alkyl group and the 5:6 bicyclic group are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.
Synthesis and PGE2 production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells
Kang, Seoung Mook,Lee, Jinsung,Jin, Jae Ho,Kim, Minju,Lee, Sunhoe,Lee, Hwi Ho,Shin, Ji-Sun,Lee, Kyung-Tae,Lee, Jae Yeol
, p. 5418 - 5422 (2015/01/08)
We present the synthesis and biological evaluation of a collection of s-triazine derivatives as a novel scaffold of compounds with the capability to inhibit the PGE2 production in LPS-induced RAW 264.7 macrophage cells. A total of 12 derivatives were synthesized and assayed for PGE2 reduction at 10 μM concentration. Two compounds (7b and 7i) exhibiting >90% inhibition of PGE2 production were found to have IC50 values of 5.76 and 5.52 μM, respectively. They were counter screened for inhibition on COX-2 activity in a cell free assay. Specifically, compound 7i (R1 = 4-Bn-Ph, R2 = Cl, R3 = Ph, R5 = CO2Me) was highly active in cells while maintaining little COX-2 inhibition (～0% at 10 μM). Molecular docking study provides the possibility that compound 7i could inhibit PGE2 production by blocking the PGH2 binding site of mPGES-1 instead of COX-2 enzyme. Based on this result, our synthetic efforts will focus on intensive structure-activity relationship (SAR) study of s-triazine scaffold to discovery a potential PGE2 synthesis inhibitor.
Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase
Thalji, Reema K.,McAtee, Jeff J.,Belyanskaya, Svetlana,Brandt, Martin,Brown, Gregory D.,Costell, Melissa H.,Ding, Yun,Dodson, Jason W.,Eisennagel, Steve H.,Fries, Rusty E.,Gross, Jeffrey W.,Harpel, Mark R.,Holt, Dennis A.,Israel, David I.,Jolivette, Larry J.,Krosky, Daniel,Li, Hu,Lu, Quinn,Mandichak, Tracy,Roethke, Theresa,Schnackenberg, Christine G.,Schwartz, Benjamin,Shewchuk, Lisa M.,Xie, Wensheng,Behm, David J.,Douglas, Stephen A.,Shaw, Ami L.,Marino Jr., Joseph P.
supporting information, p. 3584 - 3588 (2013/07/19)
1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N- {[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models.
Structure-based design of a novel series of potent, selective inhibitors of the class i phosphatidylinositol 3-kinases
Smith, Adrian L.,D'Angelo, Noel D.,Bo, Yunxin Y.,Booker, Shon K.,Cee, Victor J.,Herberich, Brad,Hong, Fang-Tsao,Jackson, Claire L. M.,Lanman, Brian A.,Liu, Longbin,Nishimura, Nobuko,Pettus, Liping H.,Reed, Anthony B.,Tadesse, Seifu,Tamayo, Nuria A.,Wurz, Ryan P.,Yang, Kevin,Andrews, Kristin L.,Whittington, Douglas A.,McCarter, John D.,Miguel, Tisha San,Zalameda, Leeanne,Jiang, Jian,Subramanian, Raju,Mullady, Erin L.,Caenepeel, Sean,Freeman, Daniel J.,Wang, Ling,Zhang, Nancy,Wu, Tian,Hughes, Paul E.,Norman, Mark H.
experimental part, p. 5188 - 5219 (2012/08/28)
A highly selective series of inhibitors of the class I phosphatidylinositol 3-kinases (PI3Ks) has been designed and synthesized. Starting from the dual PI3K/mTOR inhibitor 5, a structure-based approach was used to improve potency and selectivity, resulting in the identification of 54 as a potent inhibitor of the class I PI3Ks with excellent selectivity over mTOR, related phosphatidylinositol kinases, and a broad panel of protein kinases. Compound 54 demonstrated a robust PD-PK relationship inhibiting the PI3K/Akt pathway in vivo in a mouse model, and it potently inhibited tumor growth in a U-87 MG xenograft model with an activated PI3K/Akt pathway.
ARYL CARBOXAMIDE DERIVATIVES AS SODIUM CHANNEL INHIBITORS FOR TREATMENT OF PAIN
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Page/Page column 108, (2011/09/19)
The present invention provides compounds that are inhibitors of voltage-gated sodium channels (Nav), in particular Nav 1.7, and are therefore useful for the treatment of diseases treatable by inhibition of these channels, in particular, chronic pain disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
