5094-12-2Relevant academic research and scientific papers
HDAC6 inhibitor accelerates wound healing by inhibiting tubulin mediated IL-1β secretion in diabetic mice
Ghosh, Balaram,Goli, Sriharshini,Karnam, Kalyani,Kulkarni, Onkar Prakash,Routholla, Ganesh,Sedmaki, Kavitha,Sharma, Pravesh,Venuganti, Venkata Vamsi Krishna
, (2020/08/06)
Delayed wound healing in diabetes is characterized by sustained activation of inflammasome and increased expression of IL-1β in macrophages. Identification and validation of novel pathways to regulate IL-1β expression will provide therapeutic targets for
Double "open and Shut" Transformation of γ-Carbolines Triggered by Ammonium Salts: One-Pot Synthesis of Multiheterocyclic Compounds
Abe, Takumi,Shimizu, Haruka,Takada, Shiori,Tanaka, Takahiro,Yoshikawa, Mai,Yamada, Koji
supporting information, p. 1589 - 1592 (2018/03/23)
A novel cascade reaction of indole-2,3-epoxide equivalents with γ-carbolines by utilizing a double "open and shut" transformation to access multiheterocyclic compounds containing both isotryptamines and pyrimido[1,6-a]indoles has been developed. This strategy utilizes the in situ formation of a bulky quaternary ammonium salt via ammonium exchange, which undergoes Hofmann elimination/vinylogous Mannich/retro-Mannich/cyclization cascade sequences.
Thiapyran[4,3-b] indole compound and preparing method and application thereof
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Paragraph 0047; 0049-0051, (2018/10/19)
The invention discloses a thiapyran[4,3-b] indole compound and a preparing method and application thereof. The structure of the compound is shown in the formula 1, wherein the formula 1 is shown in the description, and R1-R5 are not all hydrogen. The compound has excellent activities of inhibiting mycelial growth, protecting detached leaves, protecting living bodies and treating the living bodiesfor rhizoctonia solani, the effects of the compound are even superior to those of positive control drugs, and the compound has an important application value in preventing and/or treating rice sheathblight.
Halogen bonding enhances activity in a series of dual 5-HT6/D2 ligands designed in a hybrid bioisostere generation/virtual screening protocol
Staroń, Jakub,Warszycki, Dawid,Kurczab, Rafa?,Sata?a, Grzegorz,Bugno, Ryszard,Hogendorf, Adam,Bojarski, Andrzej J.
, p. 54918 - 54925 (2016/07/06)
A novel hybrid bioisostere generation/virtual screening method combined with narrowing of chemical space through similarity to compounds that are active at the second target was successfully applied for the development of structurally new dual 5-HT6/D2 receptor ligands. Consequently, a series of derivatives of the found hit 1d (N-[2-(dimethylamino)ethyl]-N-(2-phenylethyl)aniline) was synthesized. The most active 5-HT6/D2 ligands also showed affinity for 5-HT7R and 5-HT2AR. The para-chloroaniline derivative was identified as a potent dual 5-HT6/5-HT7 receptor antagonist (Ki = 24 nM and Kb = 30 nM, Ki = 4 nM and Kb = 1.4 nM, respectively). In the case of halogen-containing compounds, interesting structure-activity relationships were observed at 5-HT6, D2 and 5-HT7 receptors, and the ligand-receptor complexes were subsequently examined using a molecular modelling approach that combined quantum-polarized ligand docking (QPLD) and Molecular-Mechanics-Generalized-Born/Surface Area (MM/GBSA) free-energy calculation, which permitted the identification of putative halogen binding pockets.
New route of benzyne cyclization for synthesis of 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole derivatives avoiding highly toxic aryl hydrazines
Kovacikova, Lucia,Stefek, Milan
, p. 1257 - 1263 (2015/04/27)
A new route for the regioselective synthesis of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole derivatives was developed based on cyclization of 3-chlorophenylimine-N-alkyl-4-piperidones by "the complex bases" of NaNH2 or KNH2. The procedure was performed under variable reaction conditions in inert proton-free solvents, such as THF, dioxane, 1,2-dimethoxyethane, toluene, and xylene, at temperatures varying from 20C to boiling point of the solvent used. Toxic arylhydrazine intermediates occurring in the classical Fischer indole synthesis are avoided.
HETEROCYCLIC AMIDES COMPOUNDS WHICH ARE HDAC6 INHIBITORS AND USED AS ANTI-TUMORAL AGENTS
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Paragraph 00109-00110, (2013/06/27)
The present document describes compounds of Formula I, pharmaceutical compositions comprising the same as well as methods of treating diseases such as a cancer, neurological disease, neurodegenerative disorder, stroke, traumatic brain injury, parasitic in
HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
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Page/Page column 51, (2011/02/24)
Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.
PROCESS FOR THE PREPARATION OF 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLE DERIVATIVES
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Page/Page column 5-6, (2011/11/30)
The value of the invention is the application of the cyclization of Schiff-bases of the general formula (3a-i), where R1 - R8 are substituents defined in example 1, whereby R9 = Cl using complex bases of amides of group I of the periodic table (NaNH2, KNH2) from 2.1 - 5 equiv. and alcoholates of group I of the periodic table (t-BuONa, tBuOK) from 0.05 - 2 equiv. with the advantage of application of 3 equiv. of NaNH2 and 0.05 equiv. of t-BuONa, or their mixtures with PEG (m.w. = 500 - 6000), or crown ethers, or catalysts of phase transfer lithium in inert proton-free diluents, such as benzene, cyclohexane, toluene, xylene, 1,2-dimethoxyethane, dioxane, etc., with the advantage of using THF, at a temperature from 20 °C to boiling point of the diluent used, or with the application of organo-metallic bases such as LDA, t-BuLi in inert proton-free diluents at a temperature from -80°C to 25 °C.
Ruthenium-catalyzed γ-carbolinium ion formation from aryl azides; Synthesis of dimebolin
Dong, Huijun,Latka, Regina T.,Driver, Tom G.
, p. 2726 - 2729 (2011/06/28)
A range of γ-carbolines were produced stereoselectively from ruthenium(III)-catalyzed reactions of 3-pyridyl substituted aryl azides. Other catalysts and conditions were neither as selective nor as high-yielding. This method was used to synthesize dimebolin in a concise and efficient manner.
Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A
Butler, Kyle V.,Kalin, Jay,Brochier, Camille,Vistoli, Guilio,Langley, Brett,Kozikowski, Alan P.
supporting information; experimental part, p. 10842 - 10846 (2010/09/16)
Structure-based drug design combined with homology modeling techniques were used to develop potent inhibitors of HDAC6 that display superior selectivity for the HDAC6 isozyme compared to other inhibitors. These inhibitors can be assembled in a few synthetic steps, and thus are readily scaled up for in vivo studies. An optimized compound from this series, designated Tubastatin A, was tested in primary cortical neuron cultures in which it was found to induce elevated levels of acetylated α-tubulin, but not histone, consistent with its HDAC6 selectivity. Tubastatin A also conferred dose-dependent protection in primary cortical neuron cultures against glutathione depletion-induced oxidative stress. Importantly, when given alone at all concentrations tested, this hydroxamate-containing HDAC6-selective compound displayed no neuronal toxicity, thus, forecasting the potential application of this agent and its analogues to neurodegenerative conditions.
