36684-49-8Relevant academic research and scientific papers
Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors
Bray, William,Carlin, Aaron F.,Clark, Alex E.,Endsley, Mark,Huante, Matthew B.,Huff, Sarah,Kummetha, Indrasena Reddy,Rana, Tariq M.,Smith, Davey,Tiwari, Shashi Kant,Wang, Shaobo
supporting information, (2021/10/20)
The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant SARS-CoV-2 Mpro identified six compounds that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 Mpro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit Mpro competitively. Lead E24 inhibited viral replication with a nanomolar EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells and was further confirmed to impair SARS-CoV-2 replication in human lung epithelial cells and human-induced pluripotent stem cell-derived 3D lung organoids. Altogether, these studies provide a structural framework and mechanism of Mpro inhibition that should facilitate the design of future COVID-19 treatments.
The Mpro structure-based modifications of ebselen derivatives for improved antiviral activity against SARS-CoV-2 virus
Jin, Lin,Luo, Jiajie,Qiao, Zhen,Wang, KeWei,Wei, Ningning,Zhang, Hongyi,Zhang, Yanru
, (2021/11/09)
The main protease (Mpro or 3CLpro) of SARS-CoV-2 virus is a cysteine enzyme critical for viral replication and transcription, thus indicating a potential target for antiviral therapy. A recent repurposing effort has identified ebselen, a multifunctional drug candidate as an inhibitor of Mpro. Our docking of ebselen to the binding pocket of Mpro crystal structure suggests a noncovalent interaction for improvement of potency, antiviral activity and selectivity. To test this hypothesis, we designed and synthesized ebselen derivatives aimed at enhancing their non-covalent bonds within Mpro. The inhibition of Mpro by ebselen derivatives (0.3 μM) was screened in both HPLC and FRET assays. Nine ebselen derivatives (EBs) exhibited stronger inhibitory effect on Mpro with IC50 of 0.07–0.38 μM. Further evaluation of three derivatives showed that EB2-7 exhibited the most potent inhibition of SARS-CoV-2 viral replication with an IC50 value of 4.08 μM in HPAepiC cells, as compared to the prototype ebselen at 24.61 μM. Mechanistically, EB2-7 functions as a noncovalent Mpro inhibitor in LC-MS/MS assay. Taken together, our identification of ebselen derivatives with improved antiviral activity may lead to developmental potential for treatment of COVID-19 and SARS-CoV-2 infection.
Phenylselanyl group incorporation for "glutathione peroxidase-like" activity modulation
?cianowski, Jacek,Capoccia, Lucia,Drogosz-Stachowicz, Joanna,Janecka, Anna,Obieziurska-Fabisiak, Magdalena,Pacu?a, Agata J.,Santi, Claudio
, (2020/08/06)
The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics-benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H2O2-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (-)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((-)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure-activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.
Benzisoselenazolone derivative, preparation method and application in anti-coronavirus drugs
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Paragraph 0172; 0173; 0174, (2020/12/31)
The invention belongs to the technical field of anti-coronavirus drug discovery, discloses a benzisoselenazolone derivative, a preparation method and application of the benzisoselenazolone derivativein coronavirus resistance, and relates to synthesis of a
PPh3/I2/HCOOH: An efficient CO source for the synthesis of phthalimides
Wang, Yingying,Zhou, Yang,Lei, Min,Hou, Jinjun,Jin, Qinghao,Guo, Dean,Wu, Wanying
supporting information, p. 1180 - 1185 (2019/01/26)
A straightforward and general method has been developed for the synthesis of phthalimide derivatives from 2-iodobenzamides and PPh3/I2/HCOOH in the presence of a catalytic amount of Pd(OAc)2. The reaction results demonstrate that PPh3/I2/HCOOH is a facile, efficient and safe CO source. The whole process is carried out in toluene at 80 °C and furnishes the desired products in good to excellent yields.
Synthesis of 2-(1,2,3-Triazolyl)benzamide Derivatives by a Copper(I)-Catalyzed Multicomponent Reaction
Hayeebueraheng, Abdulhakim,Kaewmee, Benyapa,Rukachaisirikul, Vatcharin,Kaeobamrung, Juthanat
, p. 6714 - 6721 (2017/12/07)
The copper-catalyzed multicomponent reaction of 2-iodobenzamides, NaN3, and terminal alkynes for the synthesis of 2-(1,2,3-triazolyl)benzamide derivatives was achieved in a one-step process over a short period of time under mild conditions. The transformation involved a C(aryl)–N bond formation process followed by an azide–alkyne cycloadditon reaction. The absence of external base was crucial for the preferred reaction pathway to occur.
Stable and Reusable Binaphthyl-Supported Palladium Catalyst for Aminocarbonylation of Aryl Iodides
Sharma, Nidhi,Sekar, Govindasamy
supporting information, p. 314 - 320 (2016/02/14)
A binaphthyl-supported Pd nanoparticles (Pd-BNP)-catalyzed aminocarbonylation of aryl iodides in the presence of carbon monoxide and amines for the synthesis of amides has been developed. This methodology provides an efficient route for the synthesis of a COX-2 enzyme inhibitor having anti-inflammatory activity.
A simple access to N-(un)substituted isoquinolin-1(2H)-ones: Unusual formation of regioisomeric isoquinolin-1(4H)-ones
Chary, R. Gangadhara,Dhananjaya,Prasad, K. Vara,Vaishaly,Ganesh,Dulla, Balakrishna,Kumar, K. Shiva,Pal, Manojit
supporting information, p. 6797 - 6800 (2014/06/23)
A ligand/additive/Pd-free Cu-mediated coupling/cyclization strategy afforded the first practical, one-pot and general approach towards synthesis of N-(un)substituted isoquinolin-1(2H)-ones. Both the catalyst and the solvent used are recyclable. The use of the Cu reagent in excess led to the unusual formation of regioisomeric and uncommon isoquinolin-1(4H)-ones. This journal is the Partner Organisations 2014.
Synthesis of (1H)-isochromen-1-imines by nickel-catalyzed reaction of 2-iodobenzamides with alkynes
Miura, Tomoya,Hiraga, Kentaro,Toyoshima, Takeharu,Yamauchi, Motoshi,Murakami, Masahiro
supporting information; experimental part, p. 798 - 800 (2012/09/07)
2-Iodobenzamides reacted with alkynes in the presence of a nickel(0)/P(4-ClC6H4)3 catalyst to produce substituted (1H)-isochromen-1-imines. The reaction proceeded through the formation of an oxanickelacycle, alkyne insertion, and reductive elimination.
Direct arylation under catalysis of an oxime-derived palladacycle: Search for a phosphane-free method
Zhang, Guofu,Zhao, Xiaobao,Yan, Yunbing,Ding, Chengrong
supporting information; experimental part, p. 669 - 672 (2012/03/27)
A phosphane-free method for the direct arylation of benzothiazole by employing oxime-derived palladacycle 1 as a catalyst was developed. The new catalyst system can be used for 2-arylations by using aryl bromides and iodides. In addition, this method is especially suitable for the intramolecular direct coupling of bromo-and iodoamides, as well aschloroamides, to achieve a rapid synthesis of benzo[c]phenanthridine alkaloids. Direct arylation reactions under catalysis of an oxime-derived palladacycle were investigated. This phosphane-free method is applicable for the 2-arylation of benzothiazole and is especially suitable for the intramolecular direct coupling of bromo-and iodoamides, as well as chloroamides, to achieve rapid synthesis of benzo[c]phenanthridine alkaloids. Copyright
