179687-79-7Relevant articles and documents
Novel heteroaryl amide derivatives as MAO-B inhibitors and pharmaceutical compositions for preventing, ameliorating or treating neurodegenerative diseases comprising the same
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Paragraph 0382; 0385-0388, (2021/04/06)
A novel heteroaryl amide derivative compound useful as MAO-B inhibitors. The present invention relates to a compound selected from a pharmaceutically acceptable salt thereof, a hydrate thereof, or a stereoisomer thereof, and a pharmaceutical composition comprising the compound as an active ingredient for preventing, alleviating, or treating neurodegenerative diseases such MAO as B's disease, 's disease, 's disease, and the like.
Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach
Lategahn, Jonas,Hardick, Julia,Grabe, Tobias,Niggenaber, Janina,Jeyakumar, Kirujan,Keul, Marina,Tumbrink, Hannah L.,Becker, Christian,Hodson, Luke,Kirschner, Tonia,Kl?vekorn, Philip,Ketzer, Julia,Baumann, Matthias,Terheyden, Susanne,Unger, Anke,Weisner, J?rn,Müller, Matthias P.,Van Otterlo, Willem A. L.,Bauer, Sebastian,Rauh, Daniel
, p. 11725 - 11755 (2020/11/26)
Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.
Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro
Jin, Shuyu,Sun, Xiuyun,Liu, Dan,Xie, Hua,Rao, Yu
, p. 1333 - 1345 (2019/05/06)
The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4?nM, SK-BR-3 IC50: 94?nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.
