27064-94-4Relevant articles and documents
A simple and efficient synthesis of the antimigraine drug lomerizine
Narsaiah, A. Venkat,Kumar, J. Kranthi
, p. 1989 - 1991 (2010)
The synthesis of the antimigraine drug 1-[bis(4-fluorophenyl)methyl]-4-(2, 3,4-trimethoxybenzyl)piperazine has been carried out in very good yields. The five-step synthesis started from bis(4-fluorophenyl)methanone. This route can be applied for large-scale preparation of lomerizine. Georg Thieme Verlag Stuttgart.
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.
Enantioselective Borylation of Aromatic C?H Bonds with Chiral Dinitrogen Ligands
Su, Bo,Zhou, Tai-Gang,Xu, Pei-Lin,Shi, Zhang-Jie,Hartwig, John F.
supporting information, p. 7205 - 7208 (2017/06/13)
The borylation of C?H bonds catalyzed by transition metals has been investigated extensively in the past two decades, but no iridium-catalyzed enantioselective borylation of C?H bonds has been reported. We report a set of iridium-catalyzed enantioselective borylations of aromatic C?H bonds. This reaction relies on a set of newly developed chiral quinolyl oxazoline ligands. This process proceeds under mild conditions with good to excellent enantioselectivity, and the borylated products can be converted to enantioenriched derivatives containing new C?O, C?C, C?Cl, or C?Br bonds.
