97023-66-0Relevant articles and documents
Synthesis and evaluation of ruthenium catalysts containing diamine-based ligands in olefin cyclopropanation
Simal, Francois,Demonceau, Albert,Noels, Alfred F.
, p. 3493 - 3496 (1998)
Ruthenium complexes with N-(p-toluenesulfonyl)-diamine ligands were found to be efficient in the catalytic cyclopropanation reaction of olefins with alkyl diazoacetate.
Structure-activity studies on N-Substituted tranylcypromine derivatives lead to selective inhibitors of lysine specific demethylase 1 (LSD1) and potent inducers of leukemic cell differentiation
Schulz-Fincke, Johannes,Hau, Mirjam,Barth, Jessica,Robaa, Dina,Willmann, Dominica,Kürner, Andreas,Haas, Julian,Greve, Gabriele,Haydn, Tinka,Fulda, Simone,Lübbert, Michael,Lüdeke, Steffen,Berg, Tobias,Sippl, Wolfgang,Schüle, Roland,Jung, Manfred
supporting information, p. 52 - 67 (2017/12/26)
FAD-dependent lysine-specific demethylase 1 (LSD1) is overexpressed or deregulated in many cancers such as AML and prostate cancer and hence is a promising anticancer target with first inhibitors in clinical trials. Clinical candidates are N-substituted derivatives of the dual LSD1-/monoamine oxidase-inhibitor tranylcypromine (2-PCPA) with a basic amine function in the N-substituent. These derivatives are selective over monoamine oxidases. So far, only very limited information on structure-activity studies about this important class of LSD1 inhibitors is published in peer reviewed journals. Here, we show that N-substituted 2-PCPA derivatives without a basic function or even a polar group are still potent inhibitors of LSD1 in vitro and effectively inhibit colony formation of leukemic cells in culture. Yet, these lipophilic inhibitors also block the structurally related monoamine oxidases (MAO-A and MAO-B), which may be of interest for the treatment of neurodegenerative disorders, but this property is undesired for applications in cancer treatment. The introduction of a polar, non-basic function led to optimized structures that retain potent LSD1 inhibitors but exhibit selectivity over MAOs and are highly potent in the suppression of colony formation of cultured leukemic cells. Cellular target engagement is shown via a Cellular Thermal Shift Assay (CETSA) for LSD1.
Generation and Reactivity of Electron-Rich Carbenes on the Surface of Catalytic Gold Nanoparticles
Oliver-Meseguer, Judit,Boronat, Mercedes,Vidal-Moya, Alejandro,Concepción, Patricia,Rivero-Crespo, Miguel ángel,Leyva-Pérez, Antonio,Corma, Avelino
supporting information, p. 3215 - 3218 (2018/03/13)
The reactive nature of carbenes can be modulated, and ultimately reversed, by receiving additional electron density from a metal. Here, it is shown that Au nanoparticles (NPs) generate an electron-rich carbene on surface after transferring electron density to the carbonyl group of an in situ activated diazoacetate, as assessed by Fourier transformed infrared (FT-IR) spectroscopy, magic angle spinning nuclear magnetic resonance (MAS NMR), and Raman spectroscopy. Density functional theory (DFT) calculations support the observed experimental values and unveil the participation of at least three different Au atoms during carbene stabilization. The surface stabilized carbene shows an extraordinary stability against nucleophiles and reacts with electrophiles to give new products. These findings showcase the ability of catalytic Au NPs to inject electron density in energetically high but symmetrically allowed valence orbitals of sluggish molecules.
