- Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage
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So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1β, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.
- Wang, Kun,Wu, Jia-Jing,Xin–Zhang,Zeng, Qing-Xuan,Zhang, Na,Huang, Wei-Jin,Tang, Sheng,Wang, Yan-Xiang,Kong, Wei-Jia,Wang, You-Chun,Li, Ying-Hong,Song, Dan-Qing
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- NOVEL HETEROCYCLYL COMPOUNDS
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The invention is concerned with novel heterocyclyl compounds of formula (I): wherein A, X, R3, R4, R5, R6, R7, R8, R9, R10, m, n and p are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor and may be used as medicaments.
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Page/Page column 25
(2010/02/17)
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- Acetohydroxamic acids
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The invention provides new acetohydroxamic acid derivatives, having interesting properties on the central nervous system, of the formula: R1 R2 R3 C-CO-NHOH, in which R2 and R3 are each hydrogen or C1-6 alkyl, and R1 is C1-6 alkyl Z1 Z2 N (where Z1 and Z2 are each phenyl, substituted phenyl, or cycloalkyl), substituted hydantoinyl, benzhydroxylcarboxamido, Z3 CH2 -- (where Z3 = optionally substituted aryl), Z4 -A- (where Z4 is optionally substituted phenyl or naphthyl, and A is --NH--, --N(C1-4 alkyl)--, --N(C5-6 cycloalkyl)--, --NHCO--, --N(C1-4 alkyl)CO--, --N(C5-6 cycloalkyl)CO--, --CONH--, --CON(C1-4 alkyl)--, --CON(C5-6 cycloalkyl)--, --NHCONH--, --N(C5 H6)CONH--, or --N(substituted phenyl)CONH--, optionally substituted benzimidazolyl, or an optionally substituted tricyclic radical, and their metal and acid addition salts.
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