198896-23-0Relevant articles and documents
Practical Intermolecular Hydroarylation of Diverse Alkenes via Reductive Heck Coupling
Gurak, John A.,Engle, Keary M.
, p. 8987 - 8992 (2018/09/11)
The hydroarylation of alkenes is an attractive approach to construct carbon-carbon (C-C) bonds from abundant and structurally diverse starting materials. Herein we report a palladium-catalyzed reductive Heck hydroarylation of aliphatic and heteroatom-substituted terminal alkenes and select internal alkenes with an array of (hetero)aryl iodides. The reaction is anti-Markovnikov selective with terminal alkenes and tolerates a wide variety of functional groups on both the alkene and (hetero)aryl coupling partners. Additionally, applications of this method to complex molecule diversifications are demonstrated. Mechanistic experiments are consistent with a mechanism in which the key alkylpalladium(II) intermediate is intercepted with formate and undergoes a decarboxylation/C-H reductive elimination cascade to afford the saturated product and turn over the cycle.
Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design
Hoang, Van-Hai,Tran, Phuong-Thao,Cui, Minghua,Ngo, Van T. H.,Ann, Jihyae,Park, Jongmi,Lee, Jiyoun,Choi, Kwanghyun,Cho, Hanyang,Kim, Hee,Ha, Hee-Jin,Hong, Hyun-Seok,Choi, Sun,Kim, Young-Ho,Lee, Jeewoo
, p. 2573 - 2590 (2017/04/03)
Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E?42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.
Preparation of azobenzenealkanethiols for self-assembled monolayers with photoswitchable properties
Krakert, Simone,Terfort, Andreas
, p. 303 - 314 (2011/06/23)
A series of azobenzenealkanethiol compounds with the structure p-RC 6H4N=NC6H4(CH2) nSH (n = 3, 4) was synthesized using a divergent strategy with the two anilines H2NC6H4(CH2) nSAc as central compounds. This strategy provides fast access to a broad variety of the respective azobenzenethiols without (note!) an oxygen atom in the alkyl chain, thus permitting the self-assembly of these compounds onto gold in a predictable conformation, also taking advantage of the previously found odd-even effect in aromatic-aliphatic hybrid systems. Initial experiments indicate that all of these molecules indeed form dense monolayers, in which the orientation of the azobenzene unit is determined by the number of methylene groups in the aliphatic part of the molecules. CSIRO 2010.
