BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis and biological evaluation of sulfonylamidines as potent c-Met inhibitors by enhancing hydrophobic interaction. 2023

Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.

The dysregulation of c-Met kinase has emerged as a significant contributing factor for the occurrence, progression, poor clinical outcomes and drug resistance of various human cancers. In our ongoing pursuit to identify promising c-Met inhibitors as potential antitumor agents, a docking study of the previously reported c-Met inhibitor 7 revealed a large unoccupied hydrophobic pocket, which could present an opportunity for further exploration of structure-activity relationships to improve the binding affinity with the allosteric hydrophobic back pocket of c-Met. Herein we performed structure-activity relationship and molecular modeling studies based on lead compound 7. The collective endeavors culminated in the discovery of compound 21j with superior efficacy to 7 and positive control foretinib by increasing the hydrophobic interaction with the hydrophobic back pocket of c-Met active site.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein

Related Publications

Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis, and biological evaluation of potent c-Met inhibitors.
September 2008, Journal of medicinal chemistry,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors.
May 2015, ACS medicinal chemistry letters,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Discovery of 3H-imidazo[4,5-b]pyridines as potent c-Met kinase inhibitors: design, synthesis, and biological evaluation.
June 2012, ChemMedChem,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors.
January 2024, Molecules (Basel, Switzerland),
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis, and biological evaluation of 4-phenoxyquinoline derivatives as potent c-Met kinase inhibitor.
December 2019, Bioorganic & medicinal chemistry letters,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis and biological evaluation of novel c-Met/HDAC dual inhibitors.
December 2020, Bioorganic & medicinal chemistry letters,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors.
September 2016, Bioorganic & medicinal chemistry,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis and biological evaluation of 6-substituted quinolines derived from cabozantinib as c-Met inhibitors.
September 2019, Archiv der Pharmazie,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis and biological evaluation of potent FAAH inhibitors.
June 2016, Bioorganic & medicinal chemistry letters,
Xiang Nan, and Xin Li, and Yanchao Wu, and Huijing Li, and Qiuxu Wang, and Shaojun Xing, and Zhigang Liang
Design, synthesis and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives as selective c-Met inhibitors.
February 2017, Bioorganic & medicinal chemistry,
Copied contents to your clipboard!