- AROMATIC HETEROCYCLIC COMPOUND, INTERMEDIATE THEREOF, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Disclosed are an aromatic heterocyclic compound, an intermediate thereof, a preparation method therefor, and a pharmaceutical composition and use thereof. The aromatic heterocyclic compound of the present invention is a new ALK5 inhibitor, and is used for treating and/or preventing various ALK5-mediated diseases.
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Paragraph 0218-0220
(2021/02/05)
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- Compound with IDH mutant inhibitory activity, preparation method and application thereof
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The invention belongs to the field of medicines, and particularly relates to a s-triazine compound with structural characteristics of a general formula I or a pharmaceutically acceptable salt thereof,a pharmaceutical composition and a preparation method thereof, and application of the s-triazine compound or the pharmaceutically acceptable salt and the pharmaceutical composition in preparation ofIDH2 mutant inhibitors. According to the invention, pharmacological experiment results show that the compound disclosed by the invention has an obvious inhibition effect on the activity of an IDH2 mutant (mIDH2), can effectively inhibit the process that alpha-ketoglutaric acid is catalyzed by mIDH2 to generate 2-hydroxyglutaric acid, and can be used for preparing drugs for preventing and/or treating various related diseases caused by IDH2 mutation, wherein the diseases comprise cancers carrying IDH2 mutation.
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- NOVEL OXALYL PIPERAZINES ACTIVE AGAINST THE HEPATITIS B VIRUS (HBV)
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The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV replication cycle, compositions comprising such compounds, methods for inhibiting HBV viral replication, methods for treating or preventing HBV infection, and processes and intermediates for making the compounds.
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Page/Page column 118
(2020/11/12)
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- NOVEL INDOLIZINE-2-CARBOXAMIDES ACTIVE AGAINST THE HEPATITIS B VIRUS (HBV)
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The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV replication cycle, compositions comprising such compounds, methods for inhibiting HBV viral replication, methods for treating or preventing HBV infection, and processes and intermediates for making the compounds.
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Page/Page column 122
(2020/11/12)
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- Exploring the Role of Coinage Metalates in Trifluoromethylation: A Combined Experimental and Theoretical Study
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Despite the known nucleophilic nature of [M(CF3)2]? (M=Cu, Ag, Au) complexes, their participation in trifluoromethylation reactions of aryl halides remains unexplored. Here, for the first time, selective access to a [Cu(CF3)2]? species is reported, which is ubiquitous in Cu-mediated trifluoromethylations, and we rationalize its complex mechanistic scenario as well as its behavior compared to its silver and gold congeners through a combination of experimental and computational approaches.
- Martínez de Salinas, Sara,Mudarra, ángel L.,Odena, Carlota,Martínez Belmonte, Marta,Benet-Buchholz, Jordi,Maseras, Feliu,Pérez-Temprano, Mónica H.
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supporting information
p. 9390 - 9394
(2019/04/03)
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- 1,3,5-TRIAZINE DERIVATIVE SALT, CRYSTAL, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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The invention discloses a crystal of 4-(tert-butoxyamino)-6-(6-(trifluoromethyl)pyridin-2-yl)-N-(2-(trifluoromethyl)pyridin-4-yl)-1,3,5-triazin-2-amine compound, a mesylate salt and crystal thereof, a preparation method thereof, a composition containing t
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Paragraph 0185; 0186; 0187
(2019/12/02)
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- Substituted triazine-based IDH inhibitor optical isomers and applications thereof
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The present invention belongs to the field of medical chemistry, and relates to a class of substituted triazine-based IDH inhibitor optical isomers and applications thereof, and specifically providesoptical isomers represented by a formula I or formula II or hydrates, solvates, crystals or pharmaceutically acceptable salts thereof, and a preparation method thereof, a pharmaceutical composition containing the optical isomers or hydrates, solvates, crystals or pharmaceutically acceptable salts thereof, and uses in treatment of cancer characterized by the presence of mutant isocitrate dehydrogenase 2. According to the present invention, the compounds have good inhibitory activity against IDH2, and can be used as the cancer treatment agents with advantages of high treatment effect and low side effect. The formulas I and II are defined in the specification.
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Paragraph 0051; 0052; 0053; 0054; 0055
(2019/02/17)
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- CHEMICAL COMPOUND OF ISOCITRATE DEHYDROGENASE INHIBITOR, AND APPLICATION THEREOF
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Provided are a chemical compound of an isocitrate dehydrogenase inhibitor, and an application thereof, belonging to the field of medicinal chemistry; specifically provided is the chemical compound represented by formula I, or its isomer, pharmaceutically acceptable salt, crystal, solvate, or prodrug, as well as their preparation methods and pharmaceutical compositions containing said chemical compound, and an application of said chemical compound or composition. The chemical compound has very good ability to inhibit mutant IDH2 enzyme activity and to inhibit mutant IDH2 neoplastic cells, and may be used for preventing and/or treating a tumor characterized by the presence of mutant IDH2.
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Paragraph 0065; 0066; 0067
(2019/06/07)
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- Crystal form of triazine IDH inhibitor methanesulfonate (by machine translation)
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The invention belongs to the field, and relates to a crystal form of mesylate of IDH inhibitor and a preparation method, and particularly relates to a crystal form of methanesulfonate of (S)-3 - (trifluoromethyl) pyridin -1 -yl) 4 - (6 - (trifluoromethyl) pyridin -2 - amino) -6 - 2 -4 -triaz -1-yl) pyrrolidine 3 -3 -2 - 5 - alcohol and a preparation method thereof, wherein the mesylate crystal form can be used for preparing a medicament for treating cancers, and a preparation method thereof. (by machine translation)
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Paragraph 0104; 0106-0108
(2019/08/07)
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- Triazine IDH inhibitor pharmaceutical salt, and preparation method thereof
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The invention belongs to the field of medicine chemistry, and relates to a triazine IDH inhibitor pharmaceutical salt or a hydrate, a solvate, or a crystal thereof, and a preparation method and applications, and more specifically relates to a pharmaceutic
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Paragraph 0079-0083
(2019/08/07)
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- Preparation method of triazine IDH inhibitor
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The invention belongs to the field of medicine chemistry, and relates to a preparation method of a triazine IDH inhibitor, and more specifically relates to a preparation method of (S)-3-(trifluoromethyl)-1-(4-(6-(trifluoromethyl)pyridine-2-yl)-6-(2-(trifl
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Paragraph 0068-0072
(2019/08/07)
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- Triazine compound, and preparation method and applications thereof
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The invention belongs to the field of medicine chemistry, and more specifically relates to a triazine compound, a preparation method thereof, and applications of the triazine compound as a reference substance in (S)-3-(trifluoromethyl)-1-(4-(6-(trifluoromethyl)pyridine-2-yl)-6-(2-(trifluoromethyl)pyridine-4-amino)-1, 3, 5-triazine-2-yl)pyrrolidine-3-ol mesylate bulk drug quality study releated impurity qualitative and/or quantitative analysis.
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Paragraph 0036; 0038-0040
(2019/08/07)
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- COMBINATION THERAPY FOR TREATING MALIGNANCIES
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Provided are methods and compositions for treating AML in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and an AML induction and consolidation therapy.
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- 1, 3, 5-TRIAZINE DERIVATIVE AND METHOD OF USING SAME
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Disclosed are compounds having formulae I and II or pharmaceutically acceptable salts or hydrates thereof, a preparation method thereof and pharmaceutical compositions thereof. The compounds having formulae I and II possesses an isocitrate dehydrogenase 2 (IDH2) inhibitory activity and are capable of treating IDH2 mutation-induced cancers.
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Paragraph 0077-0078
(2018/06/15)
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- TABLET COMPOSITIONS
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Provided herein is a tablet comprising 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol or a pharmaceutically acceptable salt thereof.
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Paragraph 0205
(2018/03/25)
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- CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
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Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
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Paragraph 1344
(2018/04/17)
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- METHODS OF PREPARING 6-(ARYL OR HETEROARYL)-1,3,5-TRIAZINE-2,4-DIOLS AND 6-(ARYL OR HETEROARYL)-1,3,5-TRIAZINE-2,4-DIAMINES
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Provided are methods of preparing compounds of formula (VIII) useful for treating cancer and intermediates of formula (I)
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Paragraph 0073; 0074
(2017/02/28)
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- COMBINATION THERAPY FOR TREATING MALIGNANCIES
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Provided are methods and compositions for treating cancers in patients carrying an IDH2 mutation using a combination of an inhibitor of a mutant IDH2 enzyme and a DNA demethylating agent.
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Paragraph 0560
(2017/05/02)
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- DEUTERATED COMPOUNDS FOR TREATING HEMATOLOGIC MALIGNANCIES, AND COMPOSITIONS AND METHODS THEREOF
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The invention provides novel chemical compounds useful for treating various hematologic malignancies, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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Paragraph 00104; 00105
(2017/05/10)
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- Trifluoromethylation of (hetero)aryl iodides and bromides with copper(i) chlorodifluoroacetate complexes
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A new copper-mediated trifluoromethylation reaction using copper(i) chlorodifluoroacetate complexes as reagents is reported. The complex [L2Cu][O2CCF2Cl] (L = bpy, dmbpy, phen) reacted with (hetero)aryl iodides and bromides in the presence of CsF in DMF at 75 °C to afford the trifluoromethylarenes in good to excellent yields. High compatibility with various chemical functions or (hetero)cycles was also observed in the reaction. A reaction mechanism involving a difluorocarbene intermediate, along with a subsequent formation of a -CF3 anion was proposed.
- Lin, Xiaoxi,Li, Zhengyu,Han, Xiaoyan,Weng, Zhiqiang
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p. 75465 - 75469
(2016/08/24)
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- Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
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This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] (1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] (2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter (ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state.
- Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
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supporting information
p. 2075 - 2084
(2016/02/12)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).
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Paragraph 00270; 00277
(2016/04/26)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are crystalline forms of 2-Methyl-l-[ (4-[ 6-(trifluoromethyl) pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2- yl)amino]propan-2-ol mesylate useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof said compound.
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Page/Page column 72; 73
(2016/09/22)
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- CRYSTALLINE FORMS OF THERAPEUTICALLY ACTIVE COMPOUNDS AND USE THEREOF
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Provided are crystalline forms of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{ [2-(trifluoromethyl)pyridin-4-yl]amino }-1, 3, 5-triazin-2-yl)amino]propan-2-ol(COMPOUND 3), 2-methyl-1-[(4- [6-(trifluoromethyl)pyridin-2-yi]-6-{ [2-(trifluoromethyl)pyridin-4- yl]amino }-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate (COMPOUND 1) and use thereof.
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Page/Page column 48
(2015/02/25)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof a compound described herein.
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Page/Page column 67
(2015/02/25)
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- N,6-BIS(ARYL OR HETEROARYL)-1,3,5-TRIAZINE-2,4-DIAMINE COMPOUNDS AS IDH2 MUTANTS INHIBITORS FOR THE TREATMENT OF CANCER
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Provided are compounds of formula (I), Wherein: ring A and ring B are each independently an optionally substituted 5-6 membered monocyclic aryl or heteroaryl. The compounds are inhibitors of isocitrate dehydrogenase 2 (IDH2) mutants useful for treating cancer.
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Page/Page column 52; 53
(2015/02/02)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Paragraph 0720-0721
(2015/02/18)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Page/Page column 156
(2015/02/02)
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- Copper-mediated perfluoroalkylation of heteroaryl bromides with (phen)CuRF
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The attachment of perfluoroalkyl groups onto organic compounds has been a major synthetic goal over the past several decades. Previously, our group reported phenanthroline-ligated perfluoroalkyl copper reagents, (phen)CuR F, which react with aryl iodides and aryl boronates to form the corresponding benzotrifluorides. Herein the perfluoroalkylation of a series of heteroaryl bromides with (phen)CuCF3 and (phen)CuCF 2CF3 is reported. The mild reaction conditions allow the process to tolerate many common functional groups. Perfluoroethylation with (phen)CuCF2CF3 occurs in somewhat higher yields than trifluoromethylation with (phen)CuCF3, creating a method to generate fluoroalkyl heteroarenes that are less accessible from trifluoroacetic acid derivatives.
- Mormino, Michael G.,Fier, Patrick S.,Hartwig, John F.
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supporting information
p. 1744 - 1747
(2014/04/17)
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- THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
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Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.
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Page/Page column 117
(2013/07/19)
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- 1,5-DIPHENYL-PYRROLIDIN-2-ONE COMPOUNDS AS CB-1 LIGANDS
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CB-1 receptor inverse agonist compounds of Formula and pharmaceutical compositions for the treatment of obesity or cognitive impairment associated with schizophrenia.
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Page/Page column 45
(2009/12/05)
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- The direct metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines
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Depending on the choice of the reagent, 2-(trifluoromethyl)-pyridine can be selectively metalated and subsequently carboxylated of otherwise functionalized either at the 3- or at the 6-position. "Optional site selectivity" can also be achieved with 4-(trifluoromethyl)pyridine, which may be deprotonated either at the 2- or at the 3-position. In contrast, 3-(trifluoromethyl)pyridine undergoes nucleophilic addition and ensuing decomposition whatever the base. Depending on the reaction conditions, 2-(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3-, 4-, or 8-positions, 3-(trifluoromethyl)quinolines at the 2- or 4-positions, and 4-(trifluoromethyl)quinoline at the 2- or 3-positions. It was therefore possible to prepare four trifluoromethyl-substituted pyridinecarboxylic acids (1, 4, 9, and 10) and six trifluoromethyl-substituted quinolinecarboxylic acids (11, 13, 14, 15, 17, and 18) regioisomerically uncontaminated and in a most straightforward way. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
- Schlosser, Manfred,Marull, Marc
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p. 1569 - 1575
(2007/10/03)
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