611-23-4Relevant articles and documents
Continuous Flow Synthesis of Azoxybenzenes by Reductive Dimerization of Nitrosobenzenes with Gel-Bound Catalysts
Schmiegel, Carsten J.,Berg, Patrik,Obst, Franziska,Schoch, Roland,Appelhans, Dietmar,Kuckling, Dirk
, p. 1628 - 1636 (2021/03/15)
In the search for a new synthetic pathway for azoxybenzenes with different substitution patterns, an approach using a microfluidic reactor with gel-bound proline organocatalysts under continuous flow is presented. Herein the formation of differently substituted azoxybezenes by reductive dimerization of nitrosobenzenes within minutes at mild conditions in good to almost quantitative yields is described. The conversion within the microfluidic reactor is analyzed and used for optimizing and validating different parameters. The effects of the different functionalities on conversion, yield, and reaction times are analyzed in detail by NMR. The applicability of this reductive dimerization is demonstrated for a wide range of differently substituted nitrosobenzenes. The effects of these different functionalities on the structure of the obtained azoxyarenes are analyzed in detail by NMR and single-crystal X-ray diffraction. Based on these results, the turnover number and the turnover frequency were determined.
"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar " Cis-On" CB1R Antagonist
Rodríguez-Soacha, Diego A.,Fender, Julia,Ramírez, Yesid A.,Collado, Juan Antonio,Mu?oz, Eduardo,Maitra, Rangan,Sotriffer, Christoph,Lorenz, Kristina,Decker, Michael
, p. 1632 - 1647 (2021/05/10)
Human cannabinoid receptor type 1 (hCB1R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and in vitro characterization of "photo-rimonabant", i.e., azo-derivatives of the selective hCB1R antagonist SR1411716A (rimonabant). By applying azo-extension strategies, we yielded compound 16a, which shows marked affinity for CB1R (Ki (cis form) = 29 nM), whose potency increases by illumination with ultraviolet light (CB1R Kitrans/cis ratio = 15.3). Through radioligand binding, calcium mobilization, and cell luminescence assays, we established that 16a is highly selective for hCB1R over hCB2R. These selective antagonists can be valuable molecular tools for optical modulation of CBRs and better understanding of disorders associated with the endocannabinoid system.
Rhodium(III)-catalyzed regioselective C–H nitrosation/annulation of unsymmetrical azobenzenes to synthesize benzotriazole N-oxides via a RhIII/RhIII redox-neutral pathway
Zhang, Yuanfei,Chen, Zhe-Ning,Su, Weiping
supporting information, (2021/05/19)
A Rh(III)-catalyzed regioselective C–H nitrosation/annulation reaction of unsymmetrical azobenzenes with [NO][BF4] has been developed to achieve high-yielding syntheses of benzotriazole N-oxides with excellent functional group tolerance. Computational studies have revealed that this oxidative C–H functionalization reaction involves an interesting redox-neutral Rh(III)/Rh(III) pathway without the change of Rh oxidation state.
Understanding Mechanistic Differences between 3-Diazoindolin-2-Imines and N-Sulfonyl-1,2,3-Triazoles in the Rh2(II)-Catalyzed Reactions with Nitrosoarenes
Bao, Xiaoguang,Fu, Rui,Gao, Ke,Kou, Luyao,Zhou, Shaofang
supporting information, p. 1565 - 1572 (2021/05/28)
The employment of α-iminometallocarbenes to construct valuable N-containing compounds has attracted significant research interest. Herein, the nucleophilic addition of nitrosoarenes with the α-imino rhodium carbene species (I), which is derived from Rh2(II)-catalyzed denitrogenation of 3-diazoindolin-2-imines, to produce synthetically useful 2-iminoindolin-nitrones is described. Mechanistically, the N-attack of nitrosoarenes with the carbene site of I is proposed. For the analogous Rh2(II)-catalyzed reaction of nitrosoarenes with N-sulfonyl-1,2,3-triazoles reported by Li and co-workers (Org. Lett. 2014, 16, 6394), however, the O-attack of nitrosoarenes with the carbene site of α-imino rhodium carbene species (II) is more favorable to occur than the N-attack. The subsequent transformation to yield the product of N-acylamidines is rationalized based on computational studies. The mechanistic differences for the reactions of nitrosoarenes with α-imino rhodium carbene species I and II are discussed.
Reversible Photoswitchable Inhibitors Generate Ultrasensitivity in Out-of-Equilibrium Enzymatic Reactions
Teders, Michael,Pogodaev, Aleksandr A.,Bojanov, Glenn,Huck, Wilhelm T. S.
supporting information, p. 5709 - 5716 (2021/05/07)
Ultrasensitivity is a ubiquitous emergent property of biochemical reaction networks. The design and construction of synthetic reaction networks exhibiting ultrasensitivity has been challenging, but would greatly expand the potential properties of life-like materials. Herein, we exploit a general and modular strategy to reversibly regulate the activity of enzymes using light and show how ultrasensitivity arises in simple out-of-equilibrium enzymatic systems upon incorporation of reversible photoswitchable inhibitors (PIs). Utilizing a chromophore/warhead strategy, PIs of the protease α-chymotrypsin were synthesized, which led to the discovery of inhibitors with large differences in inhibition constants (Ki) for the different photoisomers. A microfluidic flow setup was used to study enzymatic reactions under out-of-equilibrium conditions by continuous addition and removal of reagents. Upon irradiation of the continuously stirred tank reactor with different light pulse sequences, i.e., varying the pulse duration or frequency of UV and blue light irradiation, reversible switching between photoisomers resulted in ultrasensitive responses in enzymatic activity as well as frequency filtering of input signals. This general and modular strategy enables reversible and tunable control over the kinetic rates of individual enzyme-catalyzed reactions and makes a programmable linkage of enzymes to a wide range of network topologies feasible.
Nitrosobenzene-Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric N-Arylbenzimidazoles
An, Qian-Jin,Xia, Wang,Ding, Wei-Yi,Liu, Huan-Huan,Xiang, Shao-Hua,Wang, Yong-Bin,Zhong, Guofu,Tan, Bin
supporting information, p. 24888 - 24893 (2021/10/20)
Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2-naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo- and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C?N bond formation while the resulting amine performs the nucleophilic addition to form the second C?N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.
Tungstate-supported silica-coated magnetite nanoparticles: a novel magnetically recoverable nanocatalyst for green synthesis of nitroso arenes
Jadidi Nejad, Masoume,Yazdani, Elahe,Kazemi Miraki, Maryam,Heydari, Akbar
, p. 1575 - 1583 (2019/09/09)
Tungstate ion was heterogenized on the silica-coated magnetite nanoparticles and applied for the selective oxidation of anilines to nitroso arenes—with hydrogen peroxide/urea as oxidant in dimethyl carbonate as solvent—in moderate–good yields (40–96%). The catalyst was characterized using different techniques including Fourier-transform infrared spectroscopy, X-ray powder diffraction, vibrating sample magnetometry, scanning electron microscopy, energy dispersive X-ray and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The catalyst was easily recovered using an external magnet and reused for six times.
A Photoswitchable Agonist for the Histamine H3 Receptor, a Prototypic Family A G-Protein-Coupled Receptor
Hauwert, Niels J.,Mocking, Tamara A. M.,Da Costa Pereira, Daniel,Lion, Ken,Huppelschoten, Yara,Vischer, Henry F.,De Esch, Iwan J. P.,Wijtmans, Maikel,Leurs, Rob
supporting information, p. 4531 - 4535 (2019/03/07)
Spatiotemporal control over biochemical signaling processes involving G protein-coupled receptors (GPCRs) is highly desired for dissecting their complex intracellular signaling. We developed sixteen photoswitchable ligands for the human histamine H3 receptor (hH3R). Upon illumination, key compound 65 decreases its affinity for the hH3R by 8.5-fold and its potency in hH3R-mediated Gi protein activation by over 20-fold, with the trans and cis isomer both acting as full agonist. In real-time two-electrode voltage clamp experiments in Xenopus oocytes, 65 shows rapid light-induced modulation of hH3R activity. Ligand 65 shows good binding selectivity amongst the histamine receptor subfamily and has good photolytic stability. In all, 65 (VUF15000) is the first photoswitchable GPCR agonist confirmed to be modulated through its affinity and potency upon photoswitching while maintaining its intrinsic activity, rendering it a new chemical biology tool for spatiotemporal control of GPCR activation.
Rhodium-Catalyzed Reaction of Azobenzenes and Nitrosoarenes toward Phenazines
Xiao, Yan,Wu, Xiaopeng,Wang, Hepan,Sun, Song,Yu, Jin-Tao,Cheng, Jiang
supporting information, p. 2565 - 2568 (2019/04/30)
A rhodium-catalyzed annulative reaction between azobenzenes and nitrosoarenes has been developed, leading to a series of phenazines in moderate to good yields. This procedure proceeds with sequential chelation-assisted addition of aryl C-H to nitrosoarenes and ring closure by electrophilic attack of azo group to aryl. During this transformation, the azo group served as not only a traceless directing group but also a building block in the final products.
AHR INHIBITORS AND USES THEREOF
-
Paragraph 0422; 0423; 0432; 0433, (2019/03/02)
The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
