- Discovery of 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)ureido)-2-fluorophenoxy)-6-methoxyquinolin-7-yl)oxy)-N,N-diethylpiperidine-1-carboxamide as kinase inhibitor for the treatment of colorectal cancer
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In this study, a novel series of 4,6,7-trisubstituted quinoline analogues bearing thiazolidinones were designed and synthesized based on our previous study. Among them, the most potent compound 15i, 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-y
- Zhou, Yuting,Xu, Xingwei,Wang, Fei,He, Huan,Qi, Baohui
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- Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate
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A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.5 mg/kg). Combined with favorable in vitro potency, kinase selectivity, pharmacokinetic profile and in vivo efficacy, the promising antitumor drug candidate 20j has subsequently advanced into preclinical research.
- Chen, Tao,Fang, Wei-Rong,Huang, Wei,Li, Yun-Man,Liu, Peng-Fei,Zhuo, Lin-Sheng
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- Preparation methods of tyrosine kinase inhibitor XJF007 and its intermediate
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The invention discloses preparation methods of tyrosine kinase inhibitor XJF007 with a general structural formula (I) and its intermediate. The preparation method of the tyrosine kinase inhibitor XJF007 employs a collecting synthesis strategy of construct
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- Discovery of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors
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The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase. Through optimization and detailed SAR studies we developed low nanomolar inhibitors, and after further biological characterization we identified a potent AXL kinase inhibitor with favorable pharmacokinetic profile. The antitumor activity was determined in xenograft models, and the lead compounds reduced the tumor size by 40% with no observed toxicity as well as lung metastasis formation by 66% when compared to vehicle control.
- Szabadkai, István,Torka, Robert,Garamv?lgyi, Rita,Baska, Ferenc,Gyulavári, Pál,Boros, Sándor,Illyés, Eszter,Choidas, Axel,Ullrich, Axel,órfi, László
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p. 6277 - 6292
(2018/07/05)
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- Naphthyridine compound and pharmaceutical composition as well as applications thereof
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The invention relates to the field of biological medicines and discloses a naphthyridine compound and a pharmaceutical composition as well as applications thereof. The naphthyridine compound has a structure shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, hydrate, solvate, metabolite, a pharmaceutically acceptable salt or a prodrug. The naphthyridine compound disclosed by the invention has an anti-tumor effect which is obviously superior to the anti-tumor effect of the prior art. And moreover, the naphthyridine compound disclosed by the invention can treat diseases mediated by protein kinase.
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- Aryloxy quinoline derivatives and their use in therapy
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Disclosed herein are aryloxy quinolines derivatives,and the said compounds are compounds of formula (I) or pharmaceutically acceptable salts thereof or solvates, wherein R1, R2, R3, R4, m, n, X, Z, Ar are defined detailedly in the description. Furthermore, medicaments comprising said compounds or salts as active components and the use for treating conditions and disorders relating to protein-tyrosine kinase receptors, especially c-Met, VEGFR are also described.
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- QUINOLINYLOXYPHENYLSULFONAMIDES
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The present invention relates to quinolinyloxyphenylsulfonamides and stereoisomeric forms, solvates, hydrates and/or pharmaceutically acceptable salts of these quinolinyloxyphenylsulfonamide compounds as well as pharmaceutical compositions containing at least one of these compounds together with at least one pharmaceutically acceptable carrier, excipient and/or diluent. Said quinolinyloxyphenylsulfonamides are useful for prophylaxsis, treatment and/or after-treatment of hyperproliferative disorders, such as cancer, tumors and particularly cancer metastases.
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- C-MET MODULATORS AND METHODS OF USE
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The present invention provides compounds, which have activity for modulating protein kinase enzymatic activity and are potentially useful for modulating cellular activities such as, e.g., proliferation, differentiation, programmed cell death, migration and chemoinvasion. The present invention also provides compositions containing such compounds, and methods for producing and using such compounds and compositions.
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- C-MET MODULATORS AND METHODS OF USE
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The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate and/or modulate kinase receptor, particularly c-Met, KDR, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.
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- QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF Flt3 AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
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An objective of the present invention is to provide compounds and pharmaceticals useful for the treatment of disease where the inhibition of autophosphorylation of FMS-like tyrosine kinase 3(Flt3) is therapeutically effective. The present invention relates to a pharmaceutical composition for use in the treatment or prevention of diseases where the inhibition of autophosphorylation of Flt3 therapeutically or prophylactically effective, which comprises a compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents O or S; R1, R2, and R3 represent H, OH, or optionally substituted alkoxy; R4 represents H; R5, R6, R7, and R8 represent H, Hal, alkyl or the like; and R9 represents, e.g., alkyl substituted by t-butyl or the like.
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Page/Page column 22
(2010/02/13)
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