- Discovery of a highly potent kinase inhibitor capable of overcoming multiple imatinib-resistant ABL mutants for chronic myeloid leukemia (CML)
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As the critical driving force for chronic myeloid leukemia (CML), BCR gene fused ABL kinase has been extensively explored as a validated target of drug discovery. Although imatinib has achieved tremendous success as the first-line treatment for CML, the l
- Lu, Tingting,Cao, Jiangyan,Zou, Fengming,Li, Xixiang,Wang, Aoli,Wang, Wenliang,Liang, Huamin,Liu, Qingwang,Hu, Chen,Chen, Cheng,Hu, Zhenquan,Wang, Wenchao,Li, Lili,Ge, Jian,Shen, Yang,Ren, Tao,Liu, Jing,Xia, Ruixiang,Liu, Qingsong
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supporting information
(2021/02/26)
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- Evaluation of carbon-11 labeled 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide as PET tracer for imaging of CSF-1R expression in the brain
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Pharmacological targeting of tumor associated macrophages and microglia in the tumor microenvironment is a novel therapeutic strategy in the treatment of glioblastoma multiforme. As such, the colony stimulating factor-1 receptor (CSF-1R) has been identified as a druggable target. However, no validated companion diagnostic marker for these therapies exists to date. Towards development of a CSF-1R PET tracer, a set of six compounds based on recently reported CSF-1R inhibitor 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide (Compound 5) was designed, synthesized and evaluated in vitro for potency and selectivity. The highest affinity for CSF-1R was found for compound 5 (IC50: 2.7 nM). Subsequent radiosynthesis of [11C]5 was achieved in 2.0 ± 0.2% yield (decay corrected to start of synthesis) by carbon-11 carbon monoxide aminocarbonylation in 40 min after end of bombardment. In vitro autoradiography with [11C]5 on rat brain sections demonstrated high specific binding, but also strong off-target binding. Ex vivo, only intact tracer was observed in blood plasma at 90 min post injection in healthy rats. PET scanning results demonstrated negligible brain uptake under baseline conditions and this brain uptake did not increase by blocking of efflux transporters using Tariquidar. To conclude, [11C]5 was successfully synthesized and evaluated in healthy rats. However, the inability of [11C]5 to cross the blood-brain-barrier excludes its use for imaging of CSF-1R expression in the brain.
- Chin, Frederick T.,Kooijman, Esther J. M.,Nezam, Madina,Reyes, Samantha T.,Shen, Bin,Windhorst, Albert D.,van der Wildt, Berend
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- Spiro derivative, preparation method thereof and application of spiro derivative in medicine
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The invention relates to a spiro derivative, a preparation method thereof and application of the spiro derivative in medicine. Specifically, the invention relates to the spiro derivative shown in a general formula (I), the preparation method thereof, a pharmaceutical composition containing the spiro derivative and application of the spiro derivative as a therapeutic agent, especially application of the spiro derivative as an RAF inhibitor and application of the spiro derivative in preparation of drugs for treating or preventing various diseases (including cancers) related to over-expression RAF activity.
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Paragraph 0485; 0491-0493
(2021/08/19)
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- A novel structure of the kinase inhibitors
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The invention provides compounds of a novel kinase inhibitor as shown in the formula (I) or pharmaceutically acceptable salts, solvates, esters, acids, metabolites, combination drugs or prodrugs thereof. The compounds independently combines with at least
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Paragraph 0101; 0109; 0110
(2018/06/07)
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- Synthetic method of intermediate of flumatinib mesylate
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The invention discloses a synthetic method of an intermediate of flumatinib mesylate, and particularly relates to a preparation method of a key intermediate for synthesizing flumatinib mesylate. The initial raw material 4-methyl-3-trifluoro-methyl methyl
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Paragraph 0013; 0028-0029; 0032; 0037; 0039; 0041; 0045-0051
(2018/03/26)
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- 3-ACETYLENYL-PYRAZOLE-PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND USES THEREOF
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The present invention relates to the field of chemical and medicine, more particularly, 3-ethynylpyrazolopyrimidine derivatives and their preparation methods and uses. The invention provides a 3-ethynylpyrazolopyrimidine derivative, and the structure is shown in formula I. The present invention also provides preparation methods and use of 3-ethynylpyrazolopyrimidine derivatives, comprising the compounds and derivatives, and their pharmaceutical compositions for the use of the treatment and prevention of tumors.
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Paragraph 0172
(2017/11/10)
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- Heterocycle compound containing triazole, as well as preparation method and application of heterocycle compound
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The invention provides a heterocycle compound containing triazole, as well as a preparation method and application of the heterocycle compound. The heterocycle compound containing the triazole has a general formula in the following structure (as shown in
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Paragraph 0085; 0086
(2017/02/02)
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- 1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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The present invention relates to novel antiproliferative1H-1, 8-naphthyridin-2-ones of the general formula (I) or pharmaceutically acceptable salts thereof: In which the variable groups are as defined herein, and their preparation and use in therapeutic treatment of disorders related to inhibition of tyrosine kinases in warm blooded animals. The compounds can overcome imatinib induced drug resistance.
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Page/Page column 24; 25
(2015/12/30)
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- Mild Benzylic Monobromination of Methyl Toluates in Aqueous CTAB
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A strategy has been developed for the regioselective monobromination of methyl toluates by using tert-butylhydrogen peroxide and potassium bromide (TBHP/KBr) in a cetyltrimethylammonium bromide (CTAB) micellar medium. Ultrasonic and microwave-assisted protocols recorded increased rates and product yields under mild reaction conditions, coupled with a straightforward isolation procedure.
- Reddy, Kancharla Rajendar,Rajanna, Kamatala C.,Venkateswarlu, Marri,Saiprakash
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p. 2485 - 2487
(2015/07/27)
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- FUSED TRICYCLIC AMIDE COMPOUNDS AS MULTIPLE KINASE INHIBITORS
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Provided are fused tricyclic amide compounds, pharmaceutical compositions comprising at least one such fused tricyclic compound, processes for the preparation thereof, and the use thereof in therapy. Disclosed herein are certain tricyclic amide compounds that can be useful for inhibiting multiple (specifically BRAF and/or EGFR-T790M) kinases and for treating disorders mediated thereby.
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Page/Page column 63; 64
(2015/01/16)
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- AZAINDOLE DERIVATIVES AS INHIBITORS OF PROTEIN KINASES
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The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus a
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Page/Page column 49
(2014/07/21)
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- COMPOUND, SYNTHESIS, COMPOSITION AND USES THEREOF
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The instant application provides the disclosure for a compound of formula I, synthesis of compound of formula I and its pharmaceutical acceptable salts, as well as its polymorphs, solvates, and hydrates thereof. The pharmaceutically acceptable salt may be
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Page/Page column 9-10
(2011/11/30)
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- DERIVATIVES OF AZAINDOLES AS INHIBITORS OF PROTEIN KINASES ABL AND SRC
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The present invention relates to compounds of general formula I and use thereof as inhibitors of protein kinases AbI and Src and the method of production thereof. The present invention also relates to pharmaceutical compositions and medicinal products comprising these compounds.
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Page/Page column 96-97
(2010/09/03)
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- CHEMICAL COMPOUNDS
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The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 56
(2008/06/13)
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- Pyrazolo[1,5-A]pyrimidine derivatives and methods of use thereof
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The present invention relates to pyrazolo[1,5-a]pyrimidine derivatives, compositions comprising an effective amount of a pyrazolo[1,5-a]pyrimidine derivative and methods for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of a pyrazolo[1,5-a]pyrimidine derivative.
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Page/Page column 53
(2010/11/28)
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- FXR AGONISTS
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Compounds of formula wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.
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Page/Page column 62
(2008/06/13)
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- CHEMICAL COMPOUNDS
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The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof, of the formula (I): which possess B-Raf inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.
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Page/Page column 40
(2008/06/13)
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- QUINAZOLINONE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
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The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 81
(2008/06/13)
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