110065-66-2Relevant academic research and scientific papers
Design and Synthesis of DDR1 Inhibitors with a Desired Pharmacophore Using Deep Generative Models
Yoshimori, Atsushi,Asawa, Yasunobu,Kawasaki, Enzo,Tasaka, Tomohiko,Matsuda, Seiji,Sekikawa, Toru,Tanabe, Satoshi,Neya, Masahiro,Natsugari, Hideaki,Kanai, Chisato
, p. 955 - 958 (2021)
Discoidin domain receptor 1 (DDR1) inhibitors with a desired pharmacophore were designed using deep generative models (DGMs). DDR1 is a receptor tyrosine kinase activated by matrix collagens and implicated in diseases such as cancer, fibrosis and hypoxia. Herein we describe the synthesis and inhibitory activity of compounds generated from DGMs. Three compounds were found to have sub-micromolar inhibitory activity. The most potent of which, compound 3 (N-(4-chloro-3-((pyridin-3-yloxy)methyl)phenyl)-3-(trifluoromethyl)benzamide), had an IC50 value of 92.5 nM. Furthermore, these compounds were predicted to interact with DDR1, which have a desired pharmacophore derived from a known DDR1 inhibitor. The results of synthesis and experiments indicated that our de novo design strategy is practical for hit identification and scaffold hopping.
Synthesis and Structure-Activity Studies of a Series of salicylates as Inhibitors of EGF Receptor-Associated Tyrosine Kinase Activity
Chen, Huixiong,Boiziau, Janine,Parker, Fabienne,Maroun, Rachid,Tocque, Bruno,et al.
, p. 4094 - 4098 (2007/10/02)
The synthesis and structure-activity relationships of a series of salicylates and a series of salicylates as inhibitors of EGF receptor-associated tyrosine kinase activity are described.Their inhibitory potency was evaluated in vitro using ER 22 cell membranes (CCL 39 cells transfected with EGF receptor) as an enzyme source and the tridecapeptide RRSrc (RRLIEDAEYAARG) as substrate.Their cellular activity was measured by inhibition of the EGF-stimulated DNA synthesis of ER 22 cells.Chemical modifications were made to analyze the role of the different substituents.The amino series was found to be more active than the imino series.The hydroquinone moiety appears to be essential for tyrosine kinase inhibitory activity in the series of 5-salicylates.Comparison of the imino and amino series by molecular modeling techniques provides further evidence in support of the hypothesis that the important reduced linking chain, CH2NH allows the correct positioning of the 2,5-dihydroxybenzyl ring, possibly in a cis-like conformational arrangement.
