116419-94-4Relevant articles and documents
Discovery of a highly potent kinase inhibitor capable of overcoming multiple imatinib-resistant ABL mutants for chronic myeloid leukemia (CML)
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
, (2021)
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
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
Chin, Frederick T.,Kooijman, Esther J. M.,Nezam, Madina,Reyes, Samantha T.,Shen, Bin,Windhorst, Albert D.,van der Wildt, Berend
, (2021/06/15)
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.
Spiro derivative, preparation method thereof and application of spiro derivative in medicine
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Paragraph 0484-0489, (2021/08/19)
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.
COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
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Paragraph 0222, (2018/02/20)
Compounds of formula I defined herein act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases.
A novel structure of the kinase inhibitors
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Paragraph 0101; 0107; 0108, (2018/06/07)
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
3-ACETYLENYL-PYRAZOLE-PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND USES THEREOF
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Paragraph 0170; 0171, (2017/11/10)
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.
COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
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Paragraph 0504; 0505, (2016/09/12)
Compounds of formula I, defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for treating broncho-obstructive and inflammatory diseases.
Heterocycle compound containing triazole, as well as preparation method and application of heterocycle compound
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Paragraph 0084, (2017/02/02)
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
1H-1,8- NAPHTHYRIDIN-2ONES AS ANTI PROLIFERATIVE COMPOUNDS
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Page/Page column 24, (2015/12/30)
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.
Silver-Catalyzed C-H Trifluoromethylation of Arenes Using Trifluoroacetic Acid as the Trifluoromethylating Reagent
Shi, Guangfa,Shao, Changdong,Pan, Shulei,Yu, Jingxun,Zhang, Yanghui
, p. 38 - 41 (2015/07/28)
Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions. (Chemical Equation Presented).
