66171-50-4Relevant academic research and scientific papers
De novo Design of SARS-CoV-2 Main Protease Inhibitors
Dovala, Dustin,Fischer, Christian,Nomura, Daniel K.,Peitsinis, Zisis,Spradlin, Jessica N.,Trauner, Dirk,Yang, Chao,Zhang, Yingkai,Rühmann, Klaus-Peter,Vep?ek, Nynke A.
supporting information, (2021/10/16)
The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, M Pro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.
A new method using 1,3,5-triazine as an umpolung hydrogen cyanide equivalent toward the syntheses of isoquinolinone and 2-pyridone derivatives
Hayashida, Joji,Yoshida, Shinya
supporting information, p. 3876 - 3879 (2018/10/02)
An investigation of Hermecz and Hartenstein's cyclization methods was conducted. Overcoming the limited substrate scope allowed the expansion of the synthetic application of 1,3,5-triazine as an umpolung hydrogen cyanide equivalent. The reaction proceeded under mild conditions to provide various isoquinolinone and 2-pyridone derivatives with excellent yields.
MODIFIED COMPOUND OF ANDROGRAPHOLIDE
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Paragraph 0523-0525, (2019/01/04)
The present disclosure discloses a modified compound of andrographolide, and particularly discloses a compound shown in formula (I) and (II) or a pharmaceutically acceptable salt thereof.
Preparation method of 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound
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Paragraph 0069; 0070; 0071; 0072, (2019/01/08)
The invention provides a preparation method of a 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound. The method comprises the following steps: using a 2-hydroxy-5-bromine nitrogen-containing six-membered heterocyclic compound as a raw material, under existence of a catalyst, in atmosphere of carbon monoxide gas, using methanol as a solvent, and performing a coupling reaction to obtain a methyl 2-hydroxyl nitrogen-containing six-membered heterocyclic ring-5-carboxylate, and sequentially performing an aminolysis reaction, a chlorination reaction with phosphorus oxychloride,and an oxidation reaction to obtain the 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound. The preparation method has the advantages of short route and easily available raw material, a post-processing method is simple, no column chromatography is required after each reaction, the reaction product can be purified only by washing and extraction of a solvent, amplification is realized, industrial production is carried out, the method accords with environmental protection requirements, and has important value for actual production.
Synthesis of a series of iridium complexes bearing substituted 2-pyridonates and their catalytic performance for acceptorless dehydrogenation of alcohols under neutral conditions
Yamaguchi, Ryohei,Kobayashi, Daiki,Shimizu, Mineyuki,Fujita, Ken-ichi
supporting information, p. 14 - 19 (2017/05/19)
A series of Cp*Ir complexes bearing 5- and 4,5-substituted 2-pyridonate ligands have been synthesized and their catalytic performance for acceptorless dehydrogenation of alcohols has been investigated under neutral conditions. Electron-withdrawing groups such as methoxycarbonyl, trifluoromethyl, cyano, and nitro groups at the 5-position promoted the acceptorless dehydrogenation of 1-phenylethanol, whereas electron-donating methyl group at the 5-position retarded the reaction. Furthermore, introduction of methyl group at the 4-position improved the catalytic performance. Thus, Cp*Ir(5-trifluoromethyl-4-methyl-2-pyridonate)Cl (2bc) exhibited the highest catalytic performance among the complexes examined, and also showed good catalytic performance for acceptorless dehydrogenation of primary alcohols.
PYRAZOLYL-SUBSTITUTED PYRIDONE COMPOUNDS AS SERINE PROTEASE INHIBITORS
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Paragraph 00399-00400, (2016/04/09)
There are provided inter alia pyrazolyl-substituted pyridone compounds, which exhibit biological activity, e.g., inhibitory action, against serine proteases, including thrombin and various kallikreins. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of serine proteases, including thrombin and various kallikreins.
NOVEL ANTIFUNGAL OXODIHYDROPYRIDINECARBOHYDRAZIDE DERIVATIVE
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Paragraph 440; 441, (2015/05/06)
The present invention relates to novel oxodihydropyridinecarbohydrazide derivatives with excellent antifungal activities, an antifungal composition containing the same, and its use for the prevention and treatment of fungal infectious diseases. The oxodihydropyridinecarbohydrazide derivatives of the present invention have excellent antifungal and fungicidal activities, and thus will be useful for the prevention and treatment of various fungal infections by Candida spp., Aspergillus spp., Cryptococcus neoformans and Trichophyton spp., etc. Additionally, the oxodihydropyridinecarbohydrazide derivatives of the present invention, unlike other fungicidal preparations, can be orally administered.
Indazole-and indole-5-carboxamides: Selective and reversible monoamine oxidase B inhibitors with subnanomolar potency
Tzvetkov, Nikolay T.,Hinz, Sonja,Küppers, Petra,Gastreich, Marcus,Müller, Christa E.
supporting information, p. 6679 - 6703 (2014/11/07)
Indazole-and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4- dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC 50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4- dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4- difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A >6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.
Neonicotinic analogues: Selective antagonists for α4β2 nicotinic acetylcholine receptors
Faundez-Parraguez, Manuel,Farias-Rabelo, Nicolas,Gonzalez-Gutierrez, Juan Pablo,Etcheverry-Berrios, Alvaro,Alzate-Morales, Jans,Adasme-Carre?o, Francisco,Varas, Rodrigo,Bermudez, Isabel,Iturriaga-Vasquez, Patricio
, p. 2687 - 2694 (2013/06/27)
Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of α4β2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel α4β2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [α-125I]bungarotoxin to human α7 nAChRs and [3H]cytisine to human α4β2 nAChRs, they were markedly more potent at displacing radioligand binding to human α4β2 nAChRs than to α7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at α4β2 and α4β2α5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for α4β2 or α4β2α5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the α4/β2 subunit interfaces of α4β2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site.
Development of a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate: Trifluoromethylation on kilogram scale
Mulder, Jason A.,Frutos, Rogelio P.,Patel, Nitinchandra D.,Qu, Bo,Sun, Xiufeng,Tampone, Thomas G.,Gao, Joe,Sarvestani, Max,Eriksson, Magnus C.,Haddad, Nizar,Shen, Sherry,Song, Jinhua J.,Senanayake, Chris H.
, p. 940 - 945 (2013/07/26)
Reported herein is a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate, an intermediate in the synthesis of novel anti-infective agents. The key to this process is the trifluoromethylation of an aryl iodide using an inexpensive methyl chlorodifluoroacetate (MCDFA)/KF/CuI system, with an emphasis on the development work which led to this effective process.
