- PYRIMIDINE COMPOUND, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF
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The present invention discloses a pyrimidine compound, a preparation method thereof and a medical use thereof. Specifically, the present invention discloses a pyrimidine compound represented by formula (I), pharmaceutically acceptable salts thereof, a preparation method thereof, and a use thereof as a cyclin-dependent kinase 9 (CDK9) inhibitor, particularly for the treatment of cancer. The definition of each group in formula (I) is the same as that in the specification.
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Paragraph 0431; 0433
(2021/04/10)
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- CYCLIN-DEPENDENT KINASE INHIBITING COMPOUNDS FOR THE TREATMENT OF MEDICAL DISORDERS
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This invention is in the area of cell cycle inhibiting compounds for the treatment of disorders involving abnormal cellular proliferation, and include selective CDK2 inhibitors for medical therapy and their pharmaceutically acceptable salts and compositions.
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Page/Page column 172; 219
(2021/11/26)
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- Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model
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FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.
- Heng, Hao,Wang, Zhijie,Li, Hongmei,Huang, Yatian,Lan, Qingyuan,Guo, Xiaoxing,Zhang, Liang,Zhi, Yanle,Cai, Jiongheng,Qin, Tianren,Xiang, Li,Wang, Shuxian,Chen, Yadong,Lu, Tao,Lu, Shuai
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p. 248 - 267
(2019/05/21)
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- Design and synthesis of 4-(Heterocyclic substituted amino)-1h-pyrazole-3-carboxamide derivatives and their potent activity against acute myeloid leukemia (AML)
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Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives were designed and synthesized. Compound 8t showed strong activity against FLT3 (IC50: 0.089 nM) and CDK2/4 (IC50: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC50: 2.33 nM; CDK2/4, IC50: 1.02/0.39 nM). Compound 8t also showed excellent inhibitory activity against a variety of FLT3 mutants (IC50 50: 1.22 nM). In addition, compound 8t significantly inhibited the proliferation of most human cell lines of NCI60 (GI50 1 μM for most cell lines). Taken together, these results demonstrated the potential of 8t as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics.
- Zhi, Yanle,Wang, Zhijie,Yao, Chao,Li, Baoquan,Heng, Hao,Cai, Jiongheng,Xiang, Li,Wang, Yue,Lu, Tao,Lu, Shuai
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- Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors
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Inhibition of LRRK2 kinase activity with small molecules has emerged as a potential novel therapeutic treatment for Parkinson's disease. Herein we disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors id
- Ding, Xiao,Stasi, Luigi Piero,Ho, Ming-Hsun,Zhao, Baowei,Wang, Hailong,Long, Kai,Xu, Qiongfeng,Sang, Yingxia,Sun, Changhui,Hu, Huan,Yu, Haihua,Wan, Zehong,Wang, Lizhen,Edge, Colin,Liu, Qian,Li, Yi,Dong, Kelly,Guan, Xiaoming,Tattersall, F. David,Reith, Alastair D.,Ren, Feng
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supporting information
p. 1615 - 1620
(2018/03/29)
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- POLYARYLENE FIBER WITH IMPROVED HYDROLYTIC STABILITY
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A polyarylene fiber including 0.1-15% based on the weight of the fiber of an aromatic compound or a combination of aromatic compounds wherein each aromatic compound comprises an aromatic core and at least one of the substituents A or B, where A is represe
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Paragraph 0116; 0118
(2018/08/25)
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- Chemoselective Hydrazine-mediated Transfer Hydrogenation of Nitroarenes by Co3O4 Nanoparticles Immobilized on an Al/Si-mixed Oxide Support
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Cobalt oxide nanoparticles (size 2 to 3.5 nm) were successfully impregnated on an alumina–silica (mixed oxide) support through an experimentally viable and easily reproducible protocol. The prepared material was well characterized by XRD, HR-TEM, BET surface area, EDX and XPS analyses. Porous alumina–silica having a high surface area served as a protective heterogeneous support on which the well-dispersed Co3O4 nanoparticles served as an active catalytic species for the hydrazine-mediated transfer hydrogenation of nitroarenes. About 2 mol % of the active catalyst in ethanol at 60 °C was adequate for a successful conversion. Moreover, transfer hydrogenation of nitroarenes by the catalyst was found to take place chemoselectively in the presence of other labile functional groups such as halide, alkene, nitrile, carbonyl, and ester. This inexpensive catalyst was also able to catalyze the reaction on a gram scale reaction and found to be robust and recyclable up to eight runs.
- Reddy, P. Linga,Tripathi, Mohit,Arundhathi,Rawat, Diwan S.
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p. 785 - 791
(2017/04/13)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE
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Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are describeded, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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Paragraph 001074
(2016/12/22)
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- 2, 4 -DIAMINOPYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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The present invention relates to novel pyrimide derivatives of formula (I): that are useful as kinase inhibitors. More particularly, the present invention relates to novel pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders.
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- SUBSTITUTED QUINAZOLINE AND PYRIDO-PYRIMIDINE DERIVATIVES
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The present application provides novel substituted quinazoline and pyrido- pyrimidine compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
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Page/Page column 80
(2012/05/19)
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- 5 OXO-5,8-DIHYDROPYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS CAMKII KINASE INHIBITORS FOR TREATING CARDIOVASCULAR DISEASES
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The present invention relates to 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives, to their preparation and to their therapeutic use.
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Page/Page column 15-16
(2012/11/08)
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- Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position
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In this paper, we report the synthesis and cell-based anti-prion activity of quinacrine analogs derived by replacing the basic alkyl side chain of quinacrine with 4-(4-methylpiperazin-I-yl)phenyl, (1-benzylpiperidin-4-yl) and their structural variants. Several promising analogs were found that have a more favorable anti-prion profile than quinacrine in terms of potency and activity across different prion-infected murine cell models. They also exhibited greater binding affinities for a human prion protein fragment (hPrP121-231) than quinacrine, and had permeabilities on the PAMPA-BBB assay that fall within the range of CNS permeant candidates. When evaluated on bidirectional assays on a Pgp overexpressing cell line, one analog was less susceptible to Pgp efflux activity compared to quinacrine. Taken together, the results point to an important role for the substituted 9-amino side chain attached to the acridine, tetrahydroacridine and quinoline scaffolds. The nature of this side chain influenced cell-based potency, PAMPA permeability and binding affinity to hPrP121-231.
- Nguyen, Thuy,Sakasegawa, Yuji,Doh-Ura, Katsumi,Go, Mei-Lin
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experimental part
p. 2917 - 2929
(2011/07/08)
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- Exploration of secondary and tertiary pharmacophores in unsymmetrical N,N′-diaryl urea inhibitors of soluble epoxide hydrolase
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The impact of various secondary and tertiary pharmacophores on in vitro potency of soluble epoxide hydrolase (sEH) inhibitors based on the unsymmetrical urea scaffold 1 is discussed. N,N′-Diaryl urea inhibitors of soluble epoxide hydrolase exhibit subtle variations in inhibitory potency depending on the secondary pharmacophore but tolerate considerable structural variation in the second linker/tertiary pharmacophore fragment.
- Anandan, Sampath-Kumar,Gless, Richard D.
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scheme or table
p. 2740 - 2744
(2010/07/15)
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- CARBAZOLE AND CARBOLINE KINASE INHIBITORS
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The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) compounds inhibit tyrosine kinase activity of Jak2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
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Page/Page column 134
(2010/08/04)
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- PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS
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The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.
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Page/Page column 461
(2010/08/05)
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- Pyrrolopyrimidine Compounds and Their Uses
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The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.
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Page/Page column 43-44
(2009/12/28)
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- PYRIMIDINE-2,4-DIAMINE DERIVATIVES AND THEIR USE AS JAK2 KINASE INHIBITORS
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Pyrimidine-2,4-diamines derivatives having activity as JAK2 kinase inhibitors are disclosed, as well as pharmaceutical compositions and methods for using the same in the treatment of cancer and other JAK2 kinase-associated conditions.
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Page/Page column 23-24
(2008/12/08)
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- HETEROCYCLICALLY SUBSTITUTED INDOLINONES, THEIR PRODUCTION AND USE AS MEDICAMENTS
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The invention relates to heterocyclically substituted indolinones of general formula (I), in which R1 to R5 and X are defined as cited in claim 1, to their tautomers, diastereomers, enantiomers and to their mixtures, prodrugs and salts, in particular their physiologically compatible salts. Said compounds exhibit valuable pharmacological characteristics, in particular an inhibiting action on various receptor tyrosine kinases and cyclin-CDK complexes and on the proliferation of endothelial cells and various tumour cells. The invention also relates to medicaments containing said compounds, to the use of the latter and to a method for producing the same.
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Page/Page column 96
(2008/06/13)
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- PYRIDOPYRIMIDINE KINASE INHIBITORS
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The present invention provides compounds of formula (0): as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (0) and provides methods of treat
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- Synthesis of 1-benzoyl>-4-aryl/methyl-piperazines as CNS Active Agents
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The title compounds (IIIa-h) have been synthesised by the Mannich reaction of benzoxazolin-2-one/thione with 4-substituted 1-(p-aminobenzoyl)piperazines (IIa-d), wich in turn have been prepared by the reduction of the respective 4-substituted 1-(p-nitrobe
- Agarwal, Rajesh,Shukla, Mahesh K.,Satsangi, Rajiv K.,Chaudhary, Chapla
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p. 680 - 682
(2007/10/02)
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