849217-58-9Relevant articles and documents
Targeted protein degradation c-Met degradation agent as well as preparation method and application thereof
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, (2021/01/29)
The invention discloses a targeted protein degradation c-Met degradation agent as well as a preparation method and application thereof. The invention provides a c-Met degradation agent based on a targeted protein degradation PROTAC strategy, a preparation
Structure-guided design and development of novel N-phenylpyrimidin-2-amine derivatives as potential c-Met inhibitors
Huang, Daowei,Yang, Jixia,Zhang, Qingwei,Wang, Guan,Zhang, Zixue,Zhang, Yue,Li, Jianqi
, (2021/06/30)
The HGF/Met signaling pathway is over-expressed in many types of cancers and closely related to oncogenesis and metastasis. Thus, we developed novel N-phenylpyrimidin-2-amine derivatives to test their inhibitory activities towards c-Met kinase, and most o
Synthesis and anti-tumor activity of [1,4] dioxino [2,3-f] quinazoline derivatives as dual inhibitors of c-Met and VEGFR-2
Wei, Dengshuai,Fan, Haoru,Zheng, Kun,Qin, Xuemei,Yang, Leifu,Yang, Yajuan,Duan, Ye,Zhang, Qiang,Zeng, Chengchu,Hu, Liming
, (2019/04/27)
Both c-Met and VEGFR-2 were important targets for cancer therapies. In order to develop reversible and non-covalent c-Met and VEGFR-2 dual inhibitors, a series of [1,4]dioxino[2,3-f]quinazoline derivatives were designed and synthesized. The enzyme assay demonstrated that most target compounds had inhibition potency on both c-Met and VEGFR-2 with IC50 values in nanomolar range especially compounds 7m and 7k. Based on further cell proliferation assay in vitro, compound 7k showed significantly anti-tumor activity in vivo on a hepatocellular carcinoma (MHCC97H cells) xenograft mouse model. We docked the compound 7m with c-Met and VEGFR-2 kinases, and interpreted the SAR of these analogues. All results indicated that the target compounds were dual inhibitors of c-Met and VEGFR-2 kinases that held promising potential in cancer therapy.
Compound with sulfonyl phenylamine pyrimidine structure and application of compound as antitumor medicine
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, (2019/11/13)
The invention discloses a compound with a sulfonyl phenylamine pyrimidine structure and application of the compound as an antitumor medicine. Pharmacology experiments show that the compound has multi-target inhibition activity, has good multi-target inhib
PYRIDO-AZAHETERECYDIC COMPOUND AND PREPARATION METHOD AND USE THEREOF
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, (2018/09/21)
The present invention discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.
Substituted arylamino aromatic heterocyclic compound and application of substituted arylamino aromatic heterocyclic compound as antitumor drugs
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Paragraph 0144-0149; 0161; 0162; 0163; 0164; 0165; 0166, (2018/03/25)
The invention discloses a substituted arylamino aromatic heterocyclic compound shown in a formula (1), pharmaceutically acceptable salts thereof, a preparation method of the substituted arylamino aromatic heterocyclic compound and application of the subst
Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met/VEGFR-2
Shi, Wei,Qiang, Hao,Huang, Dandan,Bi, Xinzhou,Huang, Wenlong,Qian, Hai
, p. 814 - 831 (2018/09/29)
c-Met and VEGFR-2 have attracted interest as novel targets for treatment of various cancers. Aiming to develop potent dual c-Met and VEGFR-2 inhibitors, a series of pyrrolo[1,2-f][1,2,4]triazine derivatives were designed and synthesized. The majority of target compounds exhibited potent antiproliferative effect against c-Met addictive cancer cell lines with IC50 values ranged from 1.2 to 24.6 nM, especially 27a. In-depth studies demonstrated 27a has great selectivity to c-Met and VEGFR-2, and potent inhibitory activity against them (IC50 of 2.3 ± 0.1 nM and 5.0 ± 0.5 nM). Furthermore, it also showed the highest anticancer activity with IC50 of 0.71 ± 0.16 nM (better than the positive compound) against BaF3-TPR-Met and 37.4 ± 0.311 nM (comparable to the positive compound) against HUVEC-VEGFR2, consistent with that in c-Met sensitive tumor cell lines. Subsequently, physicochemical and pharmacokinetic characterization indicated 27a has favorable druggability and pharmacokinetic properties. Further docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, also indicating that 27a was a potential candidate for cancer therapy deserving further study.
Synthesis and biological evaluation of novel 6,11-dihydro-5H-benzo[e]pyrimido- [5,4-b][1,4]diazepine derivatives as potential c-Met inhibitors
Huang, Daowei,Huang, Lei,Zhang, Qingwei,Li, Jianqi
, p. 212 - 228 (2017/09/23)
Over expression of c-Met tyrosine kinase is known to promote tumorigenesis and metastasis, as well as to cause therapeutic resistance. Herein a series of novel 6,11-dihydro-5H-benzo[e]pyrimido[5,4-b][1,4]diazepine derivatives were designed, synthesised and evaluated for their c-Met kinase inhibition. Compounds 17e, 17f, 18a, and 18b were further examined for their anti-proliferative activities against four typical cancer cell lines (PC-3, Panc-1, HepG2, and Caki-1). The promising compound 17f was identified as a multi-target receptor tyrosine kinase inhibitor, which also displayed favourable pharmacokinetic properties in rats, had an acceptable safety profile in preclinical studies, and significant anti-tumour activity in the Caki-1 tumour xenograft model.
Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors
Li, Jieming,Gu, Weijie,Bi, Xinzhou,Li, Huilan,Liao, Chen,Liu, Chunxia,Huang, Wenlong,Qian, Hai
, p. 6674 - 6679 (2017/11/28)
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
