936-26-5Relevant articles and documents
Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles
Lopez, Marco A.,Buss, Joshua A.,Stahl, Shannon S.
supporting information, p. 597 - 601 (2022/01/20)
Site-selective chlorination of benzylic C–H bonds is achieved using a CuICl/bis(oxazoline) catalyst with N-fluorobenzenesulfonimide as the oxidant and KCl as a chloride source. This method exhibits higher benzylic selectivity, relative to estab
Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment
Alapafuja, Shakiru O.,Malamas, Michael S.,Shukla, Vidyanand,Zvonok, Alexander,Miller, Sally,Daily, Laura,Rajarshi, Girija,Miyabe, Christina Yume,Chandrashekhar, Honrao,Wood, JodiAnne,Tyukhtenko, Sergiy,Straiker, Alex,Makriyannis, Alexandros
, p. 55 - 64 (2018/11/23)
Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based 1H NMR experiments indicated that inhibitor 2 rapidly formed a covalent adduct with MGL with a residence time of about 6 h. This interconversion process “intrinsic reversibility” was exploited by modifications of the ligand's size (length and bulkiness) to generate analogs with “tunable’ adduct residence time (τ). Inhibitor 2 was evaluated in a normotensive murine model for assessing intraocular pressure (IOP), which could lead to glaucoma, a major cause of blindness. Inhibitor 2 was found to decrease ocular pressure by ～4.5 mmHg in a sustained manner for at least 12 h after a single ocular application, underscoring the potential for topically-administered MGL inhibitors as a novel therapeutic target for the treatment of glaucoma.
A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
Huy, Peter H.,Filbrich, Isabel
supporting information, p. 7410 - 7416 (2018/04/30)
A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
