50551-61-6Relevant articles and documents
Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties
Guo, Hui-Fang,Jin, Jie,Li, Zhuo-rong,Liu, Zong-ying,Xie, Zhuo-song,Xue, Si-tu,Yi, Hong,Zhang, Lei
, (2020/06/01)
The bone morphogenetic protein (BMP) pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. This study optimized the structure of the anti-osteoporosis compound 38 by balancing its lipophilicity and impr
Cyclization Reaction-Based Turn-on Probe for Covalent Labeling of Target Proteins
Fujita, Yuki,Ikebe, Yuka,Itoh, Toshimasa,Kojima, Hiroyuki,Ohashi, Nami,Takeuchi, Ryosuke,Yamamoto, Keiko
, p. 334 - 349 (2020/03/17)
Fluorescent molecules have contributed to basic biological research but there are currently only a limited number of probes available for the detection of non-enzymatic proteins. Here, we report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with multiple amino acids and exhibit a 36-fold greater emission intensity after reaction. We analyzed the reactions between TCC probes and nuclear receptors by electrospray ionization mass spectrometry, X-ray crystallography, spectrofluorometry, and fluorescence microscopy. In vitro analysis showed that probes consisting of a protein ligand and TCC could label vitamin D receptor and peroxisome proliferator-activated receptor γ. Moreover, we demonstrated that not only a ligand unit but also a peptide unit can label the target protein in a complex mixture. Non-enzymatic proteins are challenging targets for turn-on probes. Here, Kojima et al. report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with nuclear receptors and emit bright fluorescence after the reaction. TCC probes are potent tools for molecular imaging and chemical proteomics.
1-(3-(6-(3-HYDROXYNAPHTHALEN-1-YL)BENZOFURAN-2-YL)AZETIDIN-1YL)PROP-2-EN-1-ONE DERIVATIVES AND SIMILAR COMPOUNDS AS KRAS G12C MODULATORS FOR TREATING CANCER
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Page/Page column 102, (2018/08/20)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, isotopic form or stereoisomer thereof, wherein A is a five-membered heteroaryl comprising 1 or 2 non-adjacent heteroatoms, inclusive of X and Y; W, X, Y, Z, L, L1, E, R1, R2b R2c and the dotted circle are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and compounds for use in methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. Preferred compounds are e.g. l-(3-(6-(3-hydroxynaphthalen-l- yl)benzofuran-2-yl)azetidin-lyl)prop-2-en-l-one derivatives and related compounds such as e.g. the corresponding derivatives with e.g. a benzoimidazole, indole, benzooxazole, imidazopyridine or imidazole core structure, substituted on ring A by e.g. azetidine, pyrrolidine, azepane or bicyclopentane-amine (L1) each substituted by e.g. propenone (E), and the core structure substituted on the six-membered ring with e.g. 3-hydroxynaphthalene or indazole or hydroxy-, alkoxy- and/or fluoro-substituted phenyl (R1).
