893734-63-9Relevant academic research and scientific papers
Dual-Metal N-Heterocyclic Carbene Complex (M = Au and Pd)-Functionalized UiO-67 MOF for Alkyne Hydration-Suzuki Coupling Tandem Reaction
Dong, Ying,Li, Wen-Han,Dong, Yu-Bin
, p. 1818 - 1826 (2021/01/13)
Metal N-heterocyclic carbene complexes (NHC-M) have been recognized as an important class of organometallic catalysts. Herein, we demonstrate that different NHC-M (M = Au and Pd) species can be simultaneously introduced into a single metal organic framework (MOF) by direct assembly of NHC-M-decorated ligands and metal ions under solvothermal conditions. The obtained UiO-67-Au/Pd-NHBC MOF with different organometallic NHC-M species can be a highly reusable dual catalyst to sequentially promote alkyne hydration-Suzuki coupling reaction. The potential utility of this strategy is highlighted by the preparation of many more new multicatalysts of this type for various organic transformations in a sequential way.
Sulfonate Versus Sulfonate: Nickel and Palladium Multimetallic Cross-Electrophile Coupling of Aryl Triflates with Aryl Tosylates
Kang, Kai,Huang, Liangbin,Weix, Daniel J.
supporting information, p. 10634 - 10640 (2020/07/08)
While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different sulfonate esters is unknown. We report here a general solution to this challenge catalyzed by a combination of Ni and Pd with Zn reductant and LiBr as an additive. The reaction has broad scope, as demonstrated in 33 examples (65% ± 11% average yield). Mechanistic studies show that Pd strongly prefers the aryl triflate, the Ni catalyst has a small preference for the aryl tosylate, aryl transfer between catalysts is mediated by Zn, and Pd improves yields by consuming arylzinc intermediates.
Synthesis of a carbon-11 radiolabeled BACE1 inhibitor
Zhu, Yiwei,Fiedler, Stephanie A.,Hibert, Matthew L.,Wang, Changning
, p. 262 - 267 (2019/12/02)
Beta-secretase (BACE1), a transmembrane aspartyl protease, can cleave membrane-bound β-amyloid precursor proteins (APPs) to initiate the accumulation of amyloid-β (Aβ). The inhibition of BACE-1 to limit the accumulation of neurotoxic Aβ peptides could offer a potential treatment for Alzheimer’s Disease (AD). However, little is known about the distribution and density of BACE1 in the central nervous system. As a step toward filling this gap in knowledge, we have evaluated a potential radiotracer for the imaging of BACE1 using positron emission tomography (PET). A BACE1 inhibitor, 5, is reported with blood-brain barrier (BBB) permeability and high binding affinity. To characterize the pharmacokinetics and distribution of 5 in the brain, we radiolabeled 5 with carbon-11. Using PET, we found that [11C]5 shows moderate uptake in the brain when administered intravenously to rodents and further work will be performed in animal models to test its application as a PET imaging probe for the central nervous system. Our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for BACE1 inhibitors, crucial for the development of treatments for AD where CNS penetration is critical.
Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity
Ginman, Tobias,Viklund, Jenny,Malmstr?m, Jonas,Blid, Jan,Emond, Rikard,Forsblom, Rickard,Johansson, Anh,Kers, Annika,Lake, Fredrik,Sehgelmeble, Fernando,Sterky, Karin J.,Bergh, Margareta,Lindgren, Anders,Johansson, Patrik,Jeppsson, Fredrik,F?lting, Johanna,Gravenfors, Ylva,Rahm, Fredrik
supporting information, p. 4181 - 4205 (2013/07/19)
By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 μM to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.
Homocoupling of arylboronic acids catalyzed by simple gold salts
Matsuda, Takanori,Asai, Taro,Shiose, Shigeru,Kato, Kotaro
experimental part, p. 4779 - 4781 (2011/10/05)
A range of arylboronic acids undergo a homocoupling reaction in the presence of catalytic amount of gold salts to yield symmetrical biaryls. Alkenylboronic acids, arylboronic esters, and arylborates also participate in the gold-catalyzed homocoupling reaction.
