217448-53-8Relevant articles and documents
Regioselective N-Functionalization of Tautomerizable Heterocycles through Methyl Trifluoromethanesulfonate-Catalyzed Substitution of Alcohols and Alkyl Group Migrations
Biswas, Srijit,Biswas, Subrata,Duari, Surajit,Elsharif, Asma M.,Maity, Srabani,Mishra, Abhishek Kumar,Morgon, Nelson H.,Roy, Arnab,de Souza, Aguinaldo R.
supporting information, (2022/01/20)
A catalytic synthetic strategy has been developed combining two protocols, such as, direct nucleophilic substitution of alcohols followed by X- to N- alkyl group migration (X=O, S) to access N-functionalized benzoxazolones, benzothiazolethiones, indolinone, benzoimidazolethiones, and pyridinones derivatives. Methyl trifluoromethanesulfonate (MeOTf) was found to catalyze the reaction, which revealed the catalytic property of MeOTf. A mechanism was established through experiments as well as DFT calculations wherein the ?OH group of alcohols were converted to the corresponding ?OMe groups and in situ generated TfOH. The ?OMe groups produced underwent TfOH catalyzed ?X alkylation (X=O, S) of the heterocycles followed by ?X- to ?N-alkyl group migrations in a single step. (Figure presented.).
Iron-Catalyzed Reactions of 2-Pyridone Derivatives: 1,6-Addition and Formal Ring Opening/Cross Coupling
Huang, Lin,Gu, Yiting,Fürstner, Alois
supporting information, p. 4017 - 4023 (2019/08/07)
In the presence of simple iron salts, 2-pyridone derivatives react with Grignard reagents under mild conditions to give the corresponding 1,6-addition products; if the reaction medium is supplemented with an aprotic dipolar cosolvent after the actual addition step, the intermediates primarily formed succumb to ring opening, giving rise to non-thermodynamic Z,E-configured dienoic acid amide derivatives which are difficult to make otherwise. Control experiments as well as the isolation and crystallographic characterization of a (tricarbonyl)iron pyridone complex suggest that the active iron catalyst generated in situ exhibits high affinity to the polarized diene system embedded into the heterocyclic ring system of the substrates, which likely serves as the actual recognition element.
Design and Characterization of Novel Covalent Bromodomain and Extra-Terminal Domain (BET) Inhibitors Targeting a Methionine
Kharenko, Olesya A.,Patel, Reena G.,Brown, S. David,Calosing, Cyrus,White, Andre,Lakshminarasimhan, Damodharan,Suto, Robert K.,Duffy, Bryan C.,Kitchen, Douglas B.,McLure, Kevin G.,Hansen, Henrik C.,Van Der Horst, Edward H.,Young, Peter R.
, p. 8202 - 8211 (2018/09/27)
BET proteins are key epigenetic regulators that regulate transcription through binding to acetylated lysine (AcLys) residues of histones and transcription factors through bromodomains (BDs). The disruption of this interaction with small molecule bromodomain inhibitors is a promising approach to treat various diseases including cancer, autoimmune and cardiovascular diseases. Covalent inhibitors can potentially offer a more durable target inhibition leading to improved in vivo pharmacology. Here we describe the design of covalent inhibitors of BRD4(BD1) that target a methionine in the binding pocket by attaching an epoxide warhead to a suitably oriented noncovalent inhibitor. Using thermal denaturation, MALDI-TOF mass spectrometry, and an X-ray crystal structure, we demonstrate that these inhibitors selectively form a covalent bond with Met149 in BRD4(BD1) but not other bromodomains and provide durable transcriptional and antiproliferative activity in cell based assays. Covalent targeting of methionine offers a novel approach to drug discovery for BET proteins and other targets.
