- A new class of α-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities
-
Inhibitors of the proteasome have been extensively studied for their applications in the treatment of human diseases such as hematologic malignancies, autoimmune disorders, and viral infections. Many of the proteasome inhibitors reported in the literature target the non-primed site of proteasome's substrate binding pocket. In this study, we designed, synthesized and characterized a series of novel α-keto phenylamide derivatives aimed at both the primed and non-primed sites of the proteasome. In these derivatives, different substituted phenyl groups at the head group targeting the primed site were incorporated in order to investigate their structure-activity relationship and optimize the potency of α-keto phenylamides. In addition, the biological effects of modifications at the cap moiety, P1, P2 and P3 side chain positions were explored. Many derivatives displayed highly potent biological activities in proteasome inhibition and anticancer activity against a panel of six cancer cell lines, which were further rationalized by molecular modeling analyses. Furthermore, a representative α-ketoamide derivative was tested and found to be active in inhibiting the cellular infection of SARS-CoV-2 which causes the COVID-19 pandemic. These results demonstrate that this new class of α-ketoamide derivatives are potent anticancer agents and provide experimental evidence of the anti-SARS-CoV-2 effect by one of them, thus suggesting a possible new lead to develop antiviral therapeutics for COVID-19.
- An, Jing,Chen, Yiling,Ciechanover, Aaron,Fuk-Woo Chan, Jasper,Huang, Lina S.,Huang, Ziwei,Liang, Boqiang,Nie, Linlin,Wang, Juan,Warshel, Arieh,Wu, Meixian,Wu, Yi,Xu, Yan,Ye, Hui,Yuan, Shuofeng,Yuen, Kwok-Yung,Zhou, Jiao
-
-
- An Environmentally Benign, Catalyst-Free N?C Bond Cleavage/Formation of Primary, Secondary, and Tertiary Unactivated Amides
-
Herein, we report an operationally simple, cheap, and catalyst-free method for the transamidation of a diverse range of unactivated amides furnishing the desired products in excellent yields. This protocol is environmentally friendly and operates under extremely mild conditions without using any promoter or additives. Significantly, this strategy has been implied in the chemoselective synthesis of a pharmaceutical molecule, paracetamol, on a gram-scale with excellent yield. We anticipate that this universally applicable strategy will be of great interest in drug discovery, biochemistry, and organic synthesis.
- Kumar, Vishal,Dhawan, Sanjeev,Girase, Pankaj Sanjay,Singh, Parvesh,Karpoormath, Rajshekhar
-
p. 5627 - 5639
(2021/11/11)
-
- HCl-mediated transamidation of unactivated formamides using aromatic amines in aqueous media
-
We report transamidation protocol to synthesize a range of secondary and tertiary amides from weakly nucleophilic aromatic and hetero-aryl amines with low reactive formamide derivatives, utilizing hydrochloric acid as catalyst. This current acid mediated strategy is beneficial because it eliminates the need for a metal catalyst, promoter or additives in the reaction, simplifies isolation and purification. Notably, this approach conventionally used to synthesize molecules on gram scales with excellent yields and a high tolerance for functional groups.
- Dhawan, Sanjeev,Girase, Pankaj Sanjay,Kumar, Vishal,Karpoormath, Rajshekhar
-
p. 3729 - 3739
(2021/10/14)
-
- Mild C?F Activation in Perfluorinated Arenes through Photosensitized Insertion of Isonitriles at 350 nm
-
Fluorinated compounds have become important in the fields of agrochemical industry, pharmaceutical chemistry and materials sciences. Accordingly, various methods for their preparation have been developed in the past. Fluorinated compounds can be accessed via conjugation with fluorinated building blocks, via C?H fluorination or via selective activation of perfluorinated compounds to give the partially fluorinated congeners. Especially the direct activation of C?F bonds, one of the strongest σ-bonds, still remains challenging and new strategies for C?F activation are desirable. Herein a method for the photochemical activation of aromatic C?F bonds is presented. It is shown that isonitriles selectively insert into aromatic C?F bonds while aliphatic C?F bonds remain unaffected. Mechanistic studies reveal the reaction to proceed via the indirect excitation of the isonitrile to its triplet state by photoexcited acetophenone at 350 nm. Due to the relatively mild light used, the process shows high functional group tolerance and various compounds of the class of benzimidoyl fluorides are accessible from aryl isonitriles and commercially available perfluorinated arenes. (Figure presented.).
- Weidlich, Frauke,Esumi, Naoto,Chen, Dongyang,Mück-Lichtenfeld, Christian,Zysman-Colman, Eli,Studer, Armido
-
supporting information
p. 376 - 383
(2019/11/19)
-
- A Highly Water-Dispersible/Magnetically Separable Palladium Catalyst: Selective Transfer Hydrogenation or Direct Reductive N-Formylation of Nitroarenes in Water
-
Simple ion exchange of the chloride anion of an ionic-liquid-functionalized magnetic nanoparticle with [PdCl4]2- provided a highly water-dispersible and magnetically separable palladium catalyst that exhibited excellent activity toward transfer hydrogenation reactions in water as a solvent. The catalyst demonstrated outstanding performance in aqueous-phase transfer hydrogenation of various nitroarenes in a highly chemo- and regioselective manner by using HCOONH4 as a low-cost, green, and easily available hydrogen donor. Also, by using only 0.25 mol % of the catalyst and formic acid as both a hydrogen donor and formylating agent, the catalyst showed excellent activity in the one-pot, direct synthesis of N-arylformamides from nitroarenes in water as a solvent. Notably, owing to the presence of a hydrophilic ionic liquid on the surface of silica-coated iron oxide nanoparticles, the catalyst showed highly stable dispersion in water, as evidenced by the zeta potential and extremely low affinity to the organic phase. These features make this catalyst system suitable for an efficient double-separation strategy (successive extraction/final magnetic separation). The recovered aqueous phase containing the catalyst can be simply and efficiently reused in eight runs without a decrease in activity and can be easily separated from the aqueous phase at the end of the process by applying an external magnetic field.
- Karimi, Babak,Mansouri, Fariborz,Vali, Hojatollah
-
p. 1750 - 1759
(2016/01/25)
-
- Highly efficient rhodium-catalyzed transfer hydrogenation of nitroarenes into amines and formanilides
-
An efficient and selective rhodium-catalyzed transfer hydrogenation of nitroarenes with formic acid as the hydrogen source to give amines or formanilides has been developed. The addition of iodide ion accelerates the reaction, which can take place at room temperature. Georg Thieme Verlag Stuttgart New York.
- Wei, Yawen,Wu, Jianjun,Xue, Dong,Wang, Chao,Liu, Zhaotie,Zhang, Zhuozhuo,Chen, Guangfu,Xiao, Jianliang
-
supporting information
p. 1295 - 1298
(2014/06/10)
-
- Synthesis of some impurities and/or degradation products of zaleplon
-
(Chemical Equation Presented) Synthesis of several potential impurities and/or degradation products of zaleplon is identified. All the prepared compounds were unambiguously identified by NMR techniques. Spectral characteristics (IR, UV, MS) of these compo
- Radl, Stanislav,Blahovcova, Michaela,Placek, Lukas,Pekarek, Tomas,Havlicek, Jaroslav
-
experimental part
p. 276 - 283
(2010/05/18)
-
- Direct conversion of aryl nitro compounds to formanilides under catalytic transfer hydrogenation conditions
-
A direct and mild route to formanilides from aromatic nitro compounds bearing different functional groups under catalytic transfer hydrogenation (CTH) conditions is described.
- Pratap,Baskaran
-
p. 1983 - 1985
(2007/10/03)
-
- Tricyclic compounds and drug compositions containing the same
-
Compounds having a β-3 adrenaline receptor agonist and are useful as drugs for the treatment and prevention of diabetes, obesity, hyperlipemia, etc., represented by a general formula (I) and salts thereof, and a process for producing these, and their intermediates, wherein R represents hydrogen or methyl; R1 represents hydrogen, halogen, hydroxy, benzyloxy, amino, or hydroxymethyl; R2 represents hydrogen, hydroxymethyl, NHR3, SO2 NR4 R4', or nitro; R6 represents hydrogen or lower alkyl; and X represents nitrogen, R9 represents hydrogen, one of R7 and R8 represent hydrogen, and the other thereof represents hydrogen, amino, acetylamino, or hydroxy.
- -
-
-
- Aryl and heteroaryl[[7-(3-disubstituted amino)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]methanones
-
Novel aryl and heteroaryl[7-(3-substituted amino phenyl)-pyrazolo[1,5-a]pyrimidin-3-yl]methanones useful as anxiolytic, antiepileptic and sedative-hypnotic agents and as skeletal muscle relaxants, methods of using the novel compounds, compositions containing them and processes for this production.
- -
-
-
- Cephem compounds having a terminal aminocarboxylic acid grouping and containing an azacyclyl(thio)ureido group
-
Compounds of the formula STR1 in which the index n represents an integer of from 1 to 4, the index m represents 0 or 1, X represents oxygen, sulphur or the group --NH--, W represents a group --CO--, --CO--NHSO2 -- or --SO2 NH--CO--, or X-W together represent a group --CO-- or --CO--NHSO2 --, A represents optionally substituted phenylene, thienylene or furylene, Z represents oxygen or sulphur, Y represents lower alkylene, the index k represents the value 1 or 2, R4 represents hydrogen, an optionally substituted lower aliphatic or cycloaliphatic radical or acyl, R1 represents hydrogen, lower alkyl, lower alkoxy, halogen or a group of the formula --CH2 --R2 in which R2 represents a free, esterified or etherified hydroxy or mercapto group or a quaternary ammonium group, and R3 represents hydrogen or methoxy, and in which the carboxyl groups are optionally esterified in a form that can be split under physiological conditions, and salts of such compounds having salt-forming groups, are obtained by liberating the functional group(s) in a compound of the formula I in which at least one of the functional groups present is protected. The compounds are effective in vitro and in vivo against gram-positive and gram-negative bacteria and cocci.
- -
-
-