139-61-7Relevant academic research and scientific papers
A New Class of Dengue and West Nile Virus Protease Inhibitors with Submicromolar Activity in Reporter Gene DENV-2 Protease and Viral Replication Assays
Kühl, Nikos,Graf, Dominik,Bock, Josephine,Behnam, Mira A. M.,Leuthold, Mila-Mareen,Klein, Christian D.
supporting information, p. 8179 - 8197 (2020/09/21)
Dengue and West Nile virus are rapidly spreading global pathogens for which no specific therapeutic treatments are available. One of the promising targets for drug discovery against dengue and other flaviviruses is the viral serine protease NS2B-NS3. We present the design, synthesis, and in vitro and cellular characterization of a novel chemotype of potent small-molecule non-peptidic dengue protease inhibitors derived from 4-benzyloxyphenylglycine. A newly developed luciferase-based DENV-2 protease reporter system in HeLa cells (DENV2proHeLa) was employed to determine the activity of the compounds in a cellular environment. Specificity and selectivity of the DENV2proHeLa system were confirmed by viral titer reduction assays. The compounds reach low micromolar to upper nanomolar inhibitory potency in cell-based assays, are selective against other serine proteases, and do not show relevant cytotoxicity. An extensive structure-activity relationship study provides a perspective for further drug development against flaviviral infections.
Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors: Optimization of the terminal phenyl moiety of oxazolidone derivatives
Li, Yuhang,Chen, Qi,Yang, Longhe,Li, Yanting,Zhang, Yang,Qiu, Yan,Ren, Jie,Lu, Canzhong
, p. 214 - 221 (2017/08/16)
N-acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that participates in the deactivation of fatty acid ethanolamides, such as palmitoylethanolamide (PEA). NAAA inhibition may provide a potential therapeutic strategy for the treatment of diseases in which higher PEA level is desired. In the present study, we reported the structure-activity relationship (SAR) studies for oxazolidone derivatives as NAAA inhibitors. A series of substituents or alkyl replacements for the terminal phenyl ring of oxazolidone derivatives were examined. The results showed that the inhibition potency of these oxazolidone derivatives towards NAAA depends on the sizes, flexibility, and lipophilicity of the terminal groups. SAR results suggested that small lipophilic 3-phenyl substituents or hydroxy-containing 4-phenyl substituents were preferable for optimal potency. Furthermore, the distal aliphatic replacement is also preferred for high inhibitory potency. Rapid dilution and kinetic analysis suggested that oxazolidone derivatives with different terminal phenyl moieties inhibited NAAA via different mechanisms. This study identified several highly potent NAAA inhibitors, including 1a (F215, IC50 = 0.009 μM), 1o (IC50 = 0.061 μM) and 2e (IC50 = 0.092 μM), and also determined structural requirements of oxazolidone derivatives for potent inhibition against NAAA.
Highly efficient total synthesis of the clostridium-derived anti-MRSA antibiotic closthioamide
Kloss, Florian,Lincke, Thorger,Hertweck, Christian
supporting information; experimental part, p. 1429 - 1431 (2011/04/25)
The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient synthetic route. This starts from simple building blocks and involves convergent peptide coupling and polythionation. The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient route starting from simple building blocks, involving convergent peptide coupling and polythionation. Copyright
Anthranilic acid derivatives as multi drug resistance modulators
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, (2008/06/13)
Anthranilic acids of formula (I): wherein each of R to R9is an organic substituent, n is 0 or 1, m is 0 or an integer of 1 to 6, q is 0 or 1, X is a direct bond, O, S, —S—(CH2)por —O—(CHO2)p— wherein p is from 1 to 6 and Ar is an unsaturated carbocyclic or heterocyclic group, and the pharmaceutically acceptable salts thereof, have activity as inhibitors of P-glycoprotein and may thus be used, inter alia, as modulators of multidrug resistance in the treatment of multidrug resistant cancers, for example to potentiate the cytotoxicity of a cancer drug.
Arylhydroxamates useful as antiallergy agents
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, (2008/06/13)
Arylhydroxamates are provided having the structure STR1 wherein R1 is hydrogen, lower alkyl, aryl, lower alkenyl, cycloalkenyl, aralkyl, or STR2 wherein n is 1 to 4 and X is hydroxy, alkoxy, amino, C1 -C4 -alkylamino or C1 -C4 -dialkylamino. R2 is hydrogen or lower alkyl; and R3 is C1 -C20 alkyl or C3 -C20 alkenyl, aryl, aryl-alkyl, cycloalkyl, aryl-alkenyl, lower alkoxy, lower alkenyloxy, aryl-alkoxy or cycloalkyloxy. These compound are useful as inhibitors of Δ5 -lipoxygenase and as such are useful as antiallergy agents.
