22913-24-2Relevant articles and documents
Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents
Zhao, Liyu,Sun, Yin,Yin, Wenbo,Tian, Linfeng,Sun, Nannan,Zheng, Yang,Zhang, Chu,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
, (2021/11/22)
To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.
Ag(I)-Catalyzed C-H Carboxylation of Thiophene Derivatives
Lee, Mijung,Hwang, Young Kyu,Kwak, Jaesung
, p. 3136 - 3144 (2021/09/30)
CO2utilization is an attractive aspect as it allows the direct conversion of CO2into valuable chemicals. In this regard, direct incorporation of CO2into the C-H bond of heteroaromatic compounds is important due to the ubiquitous structural motifs of the heteroaromatic carboxylic acids. Herein, we report the Ag-catalyzed C-H carboxylation of thiophene derivatives. This new catalytic system involving a phosphine ligand and lithiumtert-butoxide enables the direct carboxylation of thiophenes under mild reaction conditions. Experimental studies revealed that the use oftert-butyl alkoxide is critical for the exergonic formation of an arylsilver intermediate, and the results were further supported by density functional theory calculations.
Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors
Li, Wen-Zhen,Xi, Hui-Zhi,Wang, Yi-Jie,Ma, Hong-Bo,Cheng, Zhi-Qiang,Yang, Yu,Wu, Meng-Ling,Liu, Ting-Mei,Yang, Wen,Wang, Qin,Liao, Meng-Ya,Xia, Yong,Zhang, Yi-Wen
, p. 835 - 849 (2021/09/02)
As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
Mild Copper-Catalyzed Addition of Arylboronic Esters to Di- tert -butyl Dicarbonate: An Easy Access to Methyl Arylcarboxylates
Xu, Jin-Di,Su, Xiao-Bo,Wang, Cai,Yao, Li-Wei,Liu, Jing-Hui,Hu, Guo-Qin
supporting information, p. 833 - 837 (2021/02/26)
An efficient copper-catalyzed addition of arylboronic esters to (Boc) 2O was developed. The reaction can be conducted under exceedingly mild conditions and is compatible with a variety of synthetically relevant functional groups. It therefore represents a useful alternative route for the synthesis of methyl arylcarboxylates. A preliminary mechanistic study indicated the involvement of an addition-elimination mechanism.
σ-Bond initiated generation of aryl radicals from aryl diazonium salts
Chan, Bun,McErlean, Christopher S. P.,Nashar, Philippe E.,Tatunashvili, Elene
, p. 1812 - 1819 (2020/03/17)
σ-Bond nucleophiles and molecular oxygen transform aryl diazonium salts into aryl radicals. Experimental and computational studies show that Hantzsch esters transfer hydride to aryl diazonium species, and that oxygen initiates radical fragmentation of the diazene intermediate to produce aryl radicals. The operational simplicity of this addition-fragmentation process for the generation of aryl radicals, by a polar-radical crossover mechanism, has been illustrated in a variety of bond-forming reactions.
Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
supporting information, p. 17887 - 17896 (2020/08/19)
An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
Direct Carboxylation of Electron-Rich Heteroarenes Promoted by LiO-tBu with CsF and [18]Crown-6
Shigeno, Masanori,Hanasaka, Kazuya,Sasaki, Keita,Nozawa-Kumada, Kanako,Kondo, Yoshinori
supporting information, p. 3235 - 3239 (2019/02/13)
We herein demonstrate that the combination of LiO-tBu, CsF, and [18]crown-6 efficiently promotes the direct C?H carboxylation of electron-rich heteroarenes (benzothiophene, thiophene, benzofuran, and furan derivatives). A variety of functional groups, including methyl, methoxy, halo, cyano, amide, and keto moieties, are compatible with this system. The reaction proceeds via the formation of a tert-butyl carbonate species.
Visible Light-Promoted Photocatalytic C-5 Carboxylation of 8-Aminoquinoline Amides and Sulfonamides via a Single Electron Transfer Pathway
Sen, Chiranjit,Sahoo, Tapan,Singh, Harshvardhan,Suresh, Eringathodi,Ghosh, Subhash Chandra
, p. 9869 - 9896 (2019/08/20)
An efficient photocatalytic method was developed for the remote C5-H bond carboxylation of 8-aminoquinoline amide and sulfonamide derivatives. This methodology uses in situ generated ?CBr3 radical as a carboxylation agent with alcohol and is further extended to a variety of arenes and heteroarenes to synthesize the desired carboxylated product in moderate-to-good yields. The reaction proceeding through a single electron transfer pathway was established by a control experiment, and a butylated hydroxytoluene-trapped aryl radical cation intermediate in high-resolution mass spectrometry was identified.
A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
supporting information, p. 3931 - 3943 (2018/09/11)
Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51
Zhao, Shizhen,Wei, Peng,Wu, Mengya,Zhang, Xiangqian,Zhao, Liyu,Jiang, Xiaolin,Hao, Chenzhou,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
, p. 3242 - 3253 (2018/05/23)
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC–MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14α-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability.
