475102-10-4Relevant articles and documents
Discovery of Novel Indole-Based Allosteric Highly Potent ATX Inhibitors with Great in Vivo Efficacy in a Mouse Lung Fibrosis Model
Lei, Hongrui,Guo, Ming,Li, Xiaopeng,Jia, Fang,Li, Changtao,Yang, Yu,Cao, Meng,Jiang, Nan,Ma, Enlong,Zhai, Xin
, p. 7326 - 7346 (2020)
Autotaxin (ATX) is the dominant catalytic enzyme accounting for the lipid mediator lysophosphatidic acid (LPA) through hydrolysis of lysophosphatidylcholine (LPC). There is great interest in developing nonacidic ATX inhibitors with a specific binding mode to serve as potential in vivo effective therapeutic tools. Herein, dating from a high-throughput screening (HTS) product Indole-1 (740 nM), a dedicated optimization campaign was implemented through derivatizing the-COOH group to versatile linkers that well-bridged the indole skeleton and the hydrophobic pocket binding groups. Ultimately, it was established that the coexistence of a carbamate linker and-OH-group-containing amines could generally furnish excellent indole-based ATX inhibitors with even below 1 nM in vitro activities. Two optimal entities were advanced to a bleomycin-induced mice pulmonary fibrosis model, which exerted promising efficacy in alleviating the damaged lung texture caused by bleomycin exposure. The novel carbamate-containing indole-based ATX inhibitors with a concrete binding mode may contribute to the identification of potential therapeutic agents to intervene in fibrotic diseases.
NOVEL OXADIAZOLE COMPOUNDS CONTAINING FUSED HETEROCYCLYL RINGS FOR CONTROLLING OR PREVENTING PHYTOPATHOGENIC FUNGI
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Page/Page column 71, (2021/05/15)
The present invention discloses a compound of formula (I), wherein, R1, R2, R3, R4, A1 and Q are as defined in the detailed description and a process for preparing the compound of formula (I). The present invention also discloses a method for controlling or preventing phytopathogenic fungi.
Five-membered heterocyclic oxo carboxylic acid compound and medical application thereof
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Paragraph 0952; 0957-0959, (2021/05/01)
The invention relates to a five-membered heterocyclic oxo carboxylic acid compound and a medical application thereof. Specifically, the invention relates to a compound, a pharmaceutical salt, a prodrug, a hydrate, a solvate or a crystal form as shown in a formula (I), and also relates to a preparation method of the compound, a pharmaceutical composition containing the compound and an application of the pharmaceutical composition as a secretion regulator of interferon type I, especially as an STING agonist in preparation of medicines for preventing and/or treating I-type interferon related diseases.
Improving Robustness: In Situ Generation of a Pd(0) Catalyst for the Cyanation of Aryl Bromides
Coombs, John R.,Fraunhoffer, Kenneth J.,Simmons, Eric M.,Stevens, Jason M.,Wisniewski, Steven R.,Yu, Miao
, p. 7040 - 7044 (2017/07/17)
Conditions have been developed for the palladium-catalyzed cyanation of aryl bromides utilizing the air-stable XantPhos-PdCl2 precatalyst. By employing a trialkylamine as a reducing agent, the active Pd(0) species is generated in situ, alleviating the need to employ the air-sensitive Pd2(dba)3. Twenty-two substituted benzonitriles have been synthesized using this method.
Exploration of DAPI analogues: Synthesis, antitrypanosomal activity, DNA binding and fluorescence properties
Farahat, Abdelbasset A.,Kumar, Arvind,Say, Martial,Wenzler, Tanja,Brun, Reto,Paul, Ananya,Wilson, W. David,Boykin, David W.
, p. 70 - 78 (2017/02/18)
The DAPI structure has been modified by replacing the phenyl group with substituted phenyl or heteroaryl rings. Twelve amidines were synthesized and their DNA binding, fluorescence properties, in?vitro and in?vivo activities were evaluated. These compounds are shown to bind in the DNA minor groove with high affinity, and exhibit superior in?vitro antitrypanosomal activity to that of DAPI. Six new diamidines (5b, 5c, 5d, 5e, 5f and 5j) exhibit superior in?vivo activity to that of DAPI and four of these compounds provide 100% animal cure at a low dose of 4?×?5?mg/kg i.p. in T.?b. rhodesiense infected mice. Generally, the fluorescence properties of the new analogues are inferior to that of DAPI with the exception of compound 5i which shows a moderate increase in efficacy while compound 5k is comparable to DAPI.
SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND METHODS OF CHIRAL SYNTHESIS
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Page/Page column 98-99, (2011/06/16)
Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.
Indolyne experimental and computational studies: Synthetic applications and origins of selectivities of nucleophilic additions
Im, G-Yoon J.,Bronner, Sarah M.,Goetz, Adam E.,Paton, Robert S.,Cheong, Paul H.-Y.,Houk,Garg, Neil K.
supporting information; experimental part, p. 17933 - 17944 (2011/02/26)
Efficient syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives are reported. The synthetic routes are versatile and allow access to indolyne precursors that remain unsubstituted on the pyrrole ring. Indolynes can be generated under mild fluoride-mediated conditions, trapped by a variety of nucleophilic reagents, and used to access a number of novel substituted indoles. Nucleophilic addition reactions to indolynes proceed with varying degrees of regioselectivity; distortion energies control regioselectivity and provide a simple model to predict the regioselectivity in the nucleophilic additions to indolynes and other unsymmetrical arynes. This model has led to the design of a substituted 4,5-indolyne that exhibits enhanced nucleophilic regioselectivity.
Palladium-catalyzed cross-couplings of lithium arylzincates with aromatic halides: Synthesis of analogues of isomeridianin G and evaluation as GSK-3β inhibitors
Seggio, Anne,Priem, Ghislaine,Chevallier, Floris,Mongin, Florence
experimental part, p. 3617 - 3632 (2010/03/05)
Several analogues of isomeridianin G have been synthesized using palladium-catalyzed cross-coupling reactions of lithium triorganozincates as a key step. The latter have been prepared by deprotonative lithiation followed by transmetalation using ZnCl
Synthesis of new substituted 2-(trimethylstannyl)indoles
Kumar, Arvind,Say, Martial,Boykin, David W.
, p. 707 - 710 (2008/09/21)
Synthesis of the previously unreported 2-(trimethylstannyl)indole derivatives, 5-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 6-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-5-carbonitrile, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-6-carbonitrile and 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-pyrrolo[2,3-b] pyridine-6-carbonitrile, is described. Georg Thieme Verlag Stuttgart.
Efficient N-tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate catalyzed by cesium fluoride
Inahashi, Nobuyuki,Matsumiya, Ayako,Sato, Tsuneo
, p. 294 - 296 (2008/12/21)
An environmentally friendly process for the tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate has been developed. Catalytic amount of cesium fluoride can accelerate this tert-butoxycarbonylation. Georg Thieme Verlag Stuttgart.
