- Discovery of highly potent SARS-CoV-2 Mpro inhibitors based on benzoisothiazolone scaffold
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The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.
- Chen, Weixiong,Feng, Bo,Han, Sheng,Wang, Peipei,Chen, Wuhong,Zang, Yi,Li, Jia,Hu, Youhong
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supporting information
(2022/01/14)
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- Acid-promoted palladium(II)-catalyzed ortho-halogenation of primary benzamides: En route to halo-arenes
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Br?nsted acid-promoted palladium(II)-catalyzed regioselective installation of halogens (Br, Cl, and I) to the aromatic ring of benzamide derivatives has been achieved using primary amides. A wide variety of benzamides were compatible under established conditions to afford the halogenated products without installing any external auxiliary. Mild reaction conditions, use of primary amide as a directing group, external additive-free conditions, and gram-scale reaction are some appealing features of this protocol. Detailed experimental results revealed that Br?nsted acid plays a critical role in this transformation.
- Jaiswal, Yogesh,Kumar, Amit
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- Method for synthesizing chlorantraniliprole derivative intermediate
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The invention provides a method for synthesizing a chlorantraniliprole derivative intermediate, belonging to the field of agricultural pesticides. The method comprises the following steps: subjectingthe intermediate 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid to chlorination so as to prepare 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-formyl chloride; subjecting the raw material 2-bromobenzoic acid to acylating chlorination and ammoniation so as to prepare substituted 2-bromo-benzamide; and subjecting 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-formyl chloride and substituted 2-bromo-benzamide to cyclization so as to obtain the chlorantraniliprole derivative intermediate. The method of the invention is simple and common; reagents used in the process of synthesis are low in toxicity, used solvents are recyclable, and few by-products are produced, so the method has little corrosion to equipment and low pollution to environment; since raw materials are cheap, production cost is reduced and good economical efficiency is obtained; therefore, the method has good application prospects.
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- Rapid synthesis and zebrafish evaluation of a phenanthridine-based small molecule library
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A Heck cyclisation approach is described for the rapid synthesis of a library of natural product-like small molecules, based on the phenanthridine core. The synthesis of a range of substituted benzylamine building blocks and their incorporation into the library is reported, together with a highly selective cis-dihydroxylation protocol that enables access to the target compounds in an efficient manner. Biological evaluation of the library using zebrafish phenotyping has led to the discovery of compound 20c, a novel inhibitor of early-stage zebrafish embryo development.
- Donaldson, Lauren R.,Wallace, Stephen,Haigh, David,Patton, E. Elizabeth,Hulme, Alison N.
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supporting information; experimental part
p. 2233 - 2239
(2011/04/27)
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- Certain pyrazoline derivatives with kinase inhibitory activity
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The present invention provides certain pyrazoline compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions and methods of using the compositions in the treatment of various diseases.
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Page/Page column 105
(2008/12/06)
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- 3-(3-aryloxyphenyl)-1-(substituted methyl)-s-triazine-2,4,6-oxo or thiotrione herbicidal agents
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There is provided a 3-(3-aryloxyphenyl)-1-(substituted methyl)-s-triazine-2,4,6-oxo or thiotrione compound having the structural formula I STR1 Further provided are a composition and a method comprising that compound for the control of undesirable plant s
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