147030-72-6Relevant articles and documents
An α-Cyclopropanation of Carbonyl Derivatives by Oxidative Umpolung
Bauer, Adriano,Di Mauro, Giovanni,Li, Jing,Maulide, Nuno
supporting information, p. 18208 - 18212 (2020/08/21)
The reactivity of iodine(III) reagents towards nucleophiles is often associated with umpolung and cationic mechanisms. Herein, we report a general process converting a range of ketone derivatives into α-cyclopropanated ketones by oxidative umpolung. Mechanistic investigation and careful characterization of side products revealed that the reaction follows an unexpected pathway and suggests the intermediacy of non-classical carbocations.
Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors
Chang, Shaohua,Guo, Zhuang,Li, Xue,Sun, Tianwen,Wang, Hai,Wang, Xiaowei,Wang, Yazhou,Xu, Guofeng,Xu, Tianwei,Yu, Wenying,Yu, Zhuangzhuang,Zhang, Yan,Zhao, Liwen
supporting information, (2020/05/08)
Inhibition of transforming growth factor β (TGF-β) type 1 receptor (ALK5) provides a feasible approach for the treatment of fibrotic diseases and malignant tumors. In this study, we designed and synthesized a new series of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives, and evaluated biologically as TGF-β type 1 receptor inhibitors. The most potent compound 15r inhibited the ALK5 enzyme and NIH3T3 cell viability with IC50 values of 44 and 42.5 nM, respectively. Compound 15r also displayed better oral plasma exposure and excellent bioavailability than LY-3200882, and in vivo inhibited 65.7% of the tumor growth in a CT26 xenograft mouse model.
Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents
Brindisi, Margherita,Ulivieri, Cristina,Alfano, Gloria,Gemma, Sandra,de Asís Balaguer, Francisco,Khan, Tuhina,Grillo, Alessandro,Chemi, Giulia,Menchon, Grégory,Prota, Andrea E.,Olieric, Natacha,Lucena-Agell, Daniel,Barasoain, Isabel,Diaz, J. Fernando,Nebbioso, Angela,Conte, Mariarosaria,Lopresti, Ludovica,Magnano, Stefania,Amet, Rebecca,Kinsella, Paula,Zisterer, Daniela M.,Ibrahim, Ola,O'Sullivan, Jeff,Morbidelli, Lucia,Spaccapelo, Roberta,Baldari, Cosima,Butini, Stefania,Novellino, Ettore,Campiani, Giuseppe,Altucci, Lucia,Steinmetz, Michel O.,Brogi, Simone
, p. 290 - 320 (2018/11/24)
Microtubule-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.
