36684-48-7Relevant academic research and scientific papers
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.
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.
Benzisoselenazolone derivative, preparation method and application in anti-coronavirus drugs
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Paragraph 0152; 0153; 0154, (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
, 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.
Cyrene as a bio-based solvent for HATU mediated amide coupling
Wilson, Kirsty L.,Murray, Jane,Jamieson, Craig,Watson, Allan J. B.
supporting information, p. 2851 - 2854 (2018/05/03)
Amide bonds are one of the underpinning linkages in all living systems and are fundamental within drug discovery. Current methods towards their synthesis frequently rely on the use of dipolar aprotic solvents; however, due to increasingly stringent regula
Synthesis of dibenzodiazepinones via tandem copper(I)-catalyzed C-N bond formation
Gawande, Sachin D.,Kavala, Veerababurao,Zanwar, Manoj R.,Kuo, Chun-Wei,Huang, Wen-Chang,Kuo, Ting-Shen,Huang, Hsiu-Ni,He, Chiu-Hui,Yao, Ching-Fa
, p. 2599 - 2608 (2014/09/17)
An efficient, one-pot method for the synthesis of dibenzodiazepinone derivatives involving copper-catalyzed tandem C-N bond formation is reported. The use of various halo amide and 2-iodoaniline derivatives permitted the synthesis of an array of dibenzodiazepinone derivatives in moderate to good yields. Moreover, a dibenzodiazepinone derivative {2-(11-oxo-5H-dibenzo[b,e][1, 4]diazepin-10(11H)-yl)benzonitrile} was utilized to synthesize the triazapentacyclic ring derivative {12-chloro- 8,15,22-triazapentacyclo[13.7.0. 02,7.09,14.016,21]docosa-1(22),2,4,6,9(14),10, 12,16(21),17,19-decaene}.
