19500-61-9Relevant articles and documents
Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
, (2020/12/04)
The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
Cu-Catalyzed Chemoselective Reduction of N-Heteroaromatics with NH3·BH3 in Aqueous Solution
Gao, Chao,Xuan, Qingqing,Song, Qiuling
supporting information, p. 2504 - 2508 (2021/07/31)
An efficient catalytic system was successfully developed on reduction of N-heteroaromatics with H3N?BH3 as hydrogen source in CuSO4 solution, featuring excellent chemoselectivity as well as very broad functional group tolerance. Various challenging substrates, such as OH-, NH2-, Cl-, Br-, etc., contained quinolines, quinoxalines, 1,5-naphthyridines and quinazolines were all reduced smoothly. Mechanistic studies suggested that [Cu-H] intermediate might be generated from NH3?BH3, which was believed to form with H3N?BH3 in CuSO4 solution.
Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self-assembly Chemical Library
Catalano, Marco,Moroglu, Mustafa,Balbi, Petra,Mazzieri, Federica,Clayton, James,Andrews, Katrina H.,Bigatti, Martina,Scheuermann, J?rg,Conway, Stuart J.,Neri, Dario
, p. 1752 - 1756 (2020/08/21)
DNA-encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e., single-pharmacophore libraries) or at the extremities of two complementary DNA strands (i. e., dual-pharmacophore libraries). In this work, we describe the use of a dual-pharmacophore encoded self-assembly chemical (ESAC) library for the affinity maturation of a known 4,5-dihydrobenzodiazepinone ring (THBD) acetyl-lysine (KAc) mimic for the cyclic-AMP response element binding protein (CREB) binding protein (CREBBP or CBP) bromodomain. The new pair of fragments discovered from library selection showed a sub-micromolar affinity for the CREBBP bromodomain in fluorescence polarization and ELISA assays, and selectivity against BRD4(1).
One-pot dual catalysis for the hydrogenation of heteroarenes and arenes
Chatterjee, Basujit,Kalsi, Deepti,Kaithal, Akash,Bordet, Alexis,Leitner, Walter,Gunanathan, Chidambaram
, p. 5163 - 5170 (2020/09/07)
A simple dinuclear monohydrido bridged ruthenium complex [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] acts as an efficient and selective catalyst for the hydrogenation of various heteroarenes and arenes. The nature of the catalytically active species was investigated using a combination of techniques including in situ reaction monitoring, kinetic studies, quantitative poisoning experiments and electron microscopy, evidencing a dual reactivity. The results suggest that the hydrogenation of heteroarenes proceeds via molecular catalysis. In particular, monitoring the reaction progress by NMR spectroscopy indicates that [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] is transformed into monomeric ruthenium intermediates, which upon subsequent activation of dihydrogen and hydride transfer accomplish the hydrogenation of heteroarenes under homogeneous conditions. In contrast, carbocyclic aryl motifs are hydrogenated via a heterogeneous pathway, by in situ generated ruthenium nanoparticles. Remarkably, these hydrogenation reactions can be performed using molecular hydrogen under solvent-free conditions or with 1,4-dioxane, and thus give access to a broad range of saturated heterocycles and carbocycles while generating no waste.
Ni0/Niδ+ Synergistic Catalysis on a Nanosized Ni Surface for Simultaneous Formation of C-C and C-N Bonds
Zhang, Jian,An, Zhe,Zhu, Yanru,Shu, Xin,Song, Hongyan,Jiang, Yitao,Wang, Wenlong,Xiang, Xu,Xu, Linlin,He, Jing
, p. 11438 - 11446 (2019/11/21)
Simultaneous formation of C-C/C-N bonds provides insight into the bottom-up synthesis of N-heterocycles. This work reports Ni0/Niδ+ synergistic catalysis on the surface of Ni nanoparticles for the highly efficient one-pot formation of C-C/C-N bonds, affording 1,2,3,4-tetrahydroquinoline and its derivatives from 2-amino benzyl alcohol and ethanol without any addition of liquor base or external hydrogen. Ni0/Niδ+ synergistic catalysis has been achieved by regulating the Ni particle size or activating the Ni surface with O2. In the dehydrogenation of -CH2-OH to -CH=O, the formation of C==C and C=N bonds via concurrent cross-condensation, and the transformation of C=C/C=N to C-C/C-N via hydrogen transfer, ethanol dehydrogenation has been found to be the rate-determining step. Reducing the Ni particle size effectively increases the number of surface Niδ+ sites, which accelerates catalytic dehydrogenation through synergistic catalysis between surface Niδ+ and Ni0 sites. The number of surface Niδ+ sites can be further increased by appropriately activating the Ni surface with O2
Selective hydrogenation of quinolines into 1,2,3,4-tetrahydroquinolines over a nitrogen-doped carbon-supported Pd catalyst
Ren, Yongshen,Wang, Yanxin,Li, Xun,Zhang, Zehui,Chi, Quan
, p. 16694 - 16702 (2018/10/23)
In this study, we have developed a sustainable method for the hydrogenation of quinolines to 1,2,3,4-tetrahydroquinolines under mild conditions over a nitrogen-doped carbon-supported Pd catalyst with abundant porous structures (abbreviated as Pd/CN). The mesoporous structure of the nitrogen-doped carbon support was prepared by the pyrolysis of glucose and melamine using eutectic salts of KCl and ZnCl2 as the porogen. Due to the high nitrogen content in the support, Pd nanoparticles were homogeneously dispersed on the surface of nitrogen-doped carbon materials with an ultra-small size of 1.9 nm in a narrow size distribution. The as-prepared Pd/CN catalyst showed high catalytic activity towards the hydrogenation of quinolines at 50 °C and 20 bar H2, affording the corresponding 1,2,3,4-tetrahydroquinolines with yields in the range of 86.6-97.8%. More importantly, the Pd/CN catalyst was highly stable without the loss of its catalytic activity during the recycling experiments. The use of renewable resources to prepare the catalyst makes this method promising for the sustainable 1,2,3,4-tetrahydroquinolines from the hydrogenation of quinolines.
4,5,6,7-TETRAHYDRO-1 H-PYRAZOLO[4,3-C]PYRIDIN-3-AMINE COMPOUNDS AS CBP AND/OR EP300 INHIBITORS
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Page/Page column 278, (2016/06/14)
The present invention relates to compounds of formula (I) or formula (II): and to salts thereof, wherein R1-R4 of formula (I) and R1-R3 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.
Catalytic asymmetric hydrogenation of quinoline carbocycles: Unusual chemoselectivity in the hydrogenation of quinolines
Kuwano, Ryoichi,Ikeda, Ryuhei,Hirasada, Kazuki
supporting information, p. 7558 - 7561 (2015/05/04)
The reduction of quinolines selectively took place on their carbocyclic rings to give 5,6,7,8-tetrahydroquinolines, when the hydrogenation was conducted in the presence of a Ru(η3-methallyl)2(cod)-PhTRAP catalyst. The chiral ruthenium catalyst converted 8-substituted quinolines into chiral 5,6,7,8-tetrahydroquinolines with up to 91:9 er. This journal is
Far-Red Emitting Fluorescent Dyes for Optical Nanoscopy: Fluorinated Silicon-Rhodamines (SiRF Dyes) and Phosphorylated Oxazines
Kolmakov, Kirill,Hebisch, Elke,Wolfram, Thomas,Nordwig, Lars A.,Wurm, Christian A.,Ta, Haisen,Westphal, Volker,Belov, Vladimir N.,Hell, Stefan W.
supporting information, p. 13344 - 13356 (2015/09/15)
Far-red emitting fluorescent dyes for optical microscopy, stimulated emission depletion (STED), and ground-state depletion (GSDIM) super-resolution microscopy are presented. Fluorinated silicon-rhodamines (SiRF dyes) and phosphorylated oxazines have absorption and emission maxima at about λ≈660 and 680 nm, respectively, possess high photostability, and large fluorescence quantum yields in water. A high-yielding synthetic path to introduce three aromatic fluorine atoms and unconventional conjugation/solubilization spacers into the scaffold of a silicon-rhodamine is described. The bathochromic shift in SiRF dyes is achieved without additional fused rings or double bonds. As a result, the molecular size and molecular mass stay quite small (600 Da). The use of the λ=800 nm STED beam instead of the commonly used one at λ=750-775 nm provides excellent imaging performance and suppresses re-excitation of SiRF and the oxazine dyes. The photophysical properties and immunofluorescence imaging performance of these new far-red emitting dyes (photobleaching, optical resolution, and switch-off behavior) are discussed in detail and compared with those of some well-established fluorophores with similar spectral properties. Edge of vision: Fluorinated silicon-rhodamines (SiRF dyes) and phosphorylated oxazines are applied in stimulated emission depletion (STED) and ground-state depletion microscopy (GSDIM) as new far-red-emitting fluorophores (see figure). Their photophysical properties and immunofluorescence imaging performance with a redshifted STED beam are discussed in detail and compared to those of some well-established near-IR emitting dyes.
A series of potent crebbp bromodomain ligands reveals an induced-fit pocket stabilized by a cation-π interaction
Rooney, Timothy P. C.,Filippakopoulos, Panagis,Fedorov, Oleg,Picaud, Sarah,Cortopassi, Wilian A.,Hay, Duncan A.,Martin, Sarah,Tumber, Anthony,Rogers, Catherine M.,Philpott, Martin,Wang, Minghua,Thompson, Amber L.,Heightman, Tom D.,Pryde, David C.,Cook, Andrew,Paton, Robert S.,Mueller, Susanne,Knapp, Stefan,Brennan, Paul E.,Conway, Stuart J.
, p. 6126 - 6130 (2014/06/23)
The benzoxazinone and dihydroquinoxalinone fragments were employed as novel acetyl lysine mimics in the development of CREBBP bromodomain ligands. While the benzoxazinone series showed low affinity for the CREBBP bromodomain, expansion of the dihydroquino
