- Exploration of benzofuran-based compounds as potent and selective Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3) inhibitors
-
Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3) has been identified as a potential target for the development of novel drugs against multi-drug resistant malaria. A series of benzofuran-based compounds was synthesised and evaluated as inhibitors of recombinantly expressed and purified PfGSK-3 and human glycogen synthase kinase-3 beta (HsGSK-3β). Of this series, five compounds (5k, 5m, 5p, 5r, 5s) preferentially inhibited PfGSK-3, with four of these compounds exhibiting IC50 values in the sub-micromolar range (0.00048–0.440 μM). Evaluation of the structure-activity relationships required for PfGSK-3 selective inhibition indicated that a C6-OCH3 substitution on ring A is preferred, while the effect of the ring B substituent on activity, in decreasing order is: C4′-CN > C4′-F > C3′-OCH3 > C3′,4′-diCl. To date, development of PfGSK-3 inhibitors has been limited to the 4-phenylthieno[2,3-b]pyridine class. Chalcone-based scaffolds, such as the benzofurans described herein, are promising new hits which can be explored for future design of PfGSK-3 selective inhibitors.
- Moolman, Chantalle,van der Sluis, Rencia,Beteck, Richard M.,Legoabe, Lesetja J.
-
-
- Synthesis and anti-methicillin-resistant Staphylococcus aureus activity of 5,7-dibromo-2-benzoylbenzofurans alone and in combination with antibiotics
-
A series of 5,7-dibromo-2-benzoylbenzofurans were synthesized by the Rap–Stoermer condensation of 5,7-dibromosalicylaldehyde with diverse phenacyl bromides and evaluated for in-vitro antibacterial activities against methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and MRSA ATCC 33591 by agar dilution method. The synergistic effects were determined by using the agar dilution checkerboard assay. The derivatives bearing carboxylic acid functional groups exhibited reasonable activity against MRSA strains with the best MIC = 32 μg/mL (9b, 9d). Moreover, the additive or synergistic interactions against MRSA strains was observed in six combinations (1b + cefuroxime/gentamicin, 1c + ciprofloxacin/gentamicin, 9b + gentamicin, and 9c + ciprofloxacin) with the fractional inhibitory concentration index (FICI) values in the range of 0.375–1.0. Significantly, the MICs of these antibiotics were reduced 2–4-fold. The results of the MTT assay illustrated the low mammalian cell cytotoxicity of these potent compounds.
- Phan, Phuong-Thuy T.,Nguyen, Hong-Nhung T.,Kim, Son N.,Pham, Tuan-Anh N.
-
supporting information
p. 786 - 796
(2020/12/09)
-
- Microwave-assisted multicomponent synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives
-
We present an efficient one-pot, three component microwave-assisted synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives starting from benzo[f]quinoline, 2-bromo-acetophenones or 2-chloro-(N-phenyl)acetamides and electron-deficient alkynes. This synthetic strategy provides a direct and easy access to a range of novel benzo[f]pyrrolo[1,2-a]quinoline derivatives. The method has the advantages of considerable shorter reaction time, reduced solvent consumption, operational simplicity and minimal impact on the environment. Nine new benzo[f]pyrrolo[1,2-a]quinoline derivatives have been synthesized with the new method and they are fully characterized.
- Georgescu, Emilian,Georgescu, Florentina,Dumitrascu, Florea,Draghici, Constantin,Nicolescu, Alina,Marinescu, Daniela,Deleanu, Calin
-
-
- Benzoic acid resin (BAR): a heterogeneous redox organocatalyst for continuous flow synthesis of benzoquinones from β-O-4 lignin models
-
A polymer-bound organocatalyst for Baeyer-Villiger reaction and phenol oxidation under continuous flow conditions is described for the first time.BARhas revealed two catalytic activities that enabled the generation of a novel approach for the synthesis of benzoquinones from β-O-4 lignin models in a one-pot protocol. High catalytic activities (yields up to 98%), selectivities, recyclability and productivity were achieved.
- Dias, Kevin de Aquino,Pereira Junior, Marcus Vinicius Pinto,Andrade, Leandro Helgueira
-
supporting information
p. 2308 - 2316
(2021/04/07)
-
- Chiral Bidentate Phosphoramidite-Pd Catalyzed Asymmetric Decarboxylative Dipolar Cycloaddition for Multistereogenic Tetrahydrofurans with Cyclic N-Sulfonyl Ketimine Moieties
-
An asymmetric [3 + 2] cycloaddition of vinyl ethylenecarbonates (VECs) and (E)-3-arylvinyl substituted benzo[d] isothiazole 1,1-dioxides has been developed using the Pd complex of a bidentate phosphoramidite (Me-BIPAM) as the catalyst, providing a wide variety of chiral multistereogenic vinyltetrahydrofurans in good yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee).
- Lv, Hao-Peng,Yang, Xiao-Peng,Wang, Bai-Lin,Yang, Hao-Di,Wang, Xing-Wang,Wang, Zheng
-
supporting information
p. 4715 - 4720
(2021/06/28)
-
- Nickel-catalyzed asymmetric arylative cyclization of N-alkynones: Efficient access to 1,2,3,6-tetrahydropyridines with a tertiary alcohol
-
Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues.
- He, Lin,Li, Ruihao,Li, Wendian,Lv, Hui,Tian, Jiangyan
-
supporting information
(2021/07/06)
-
- Oxidation Potential-Guided Electrochemical Radical-Radical Cross-Coupling Approaches to 3-Sulfonylated Imidazopyridines and Indolizines
-
Oxidation potential-guided electrochemical radical-radical cross-coupling reactions between N-heteroarenes and sodium sulfinates have been established. Thus, simple cyclic voltammetry measurement of substrates predicts the likelihood of successful radical-radical coupling reactions, allowing the simple and direct synthetic access to 3-sulfonylated imidazopyridines and indolizines. The developed electrochemical radical-radical cross-coupling reactions to sulfonylated N-heteroarenes boast the green synthetic nature of the reactions that are oxidant- and metal-free.
- Kim, Wansoo,Kim, Hun Young,Oh, Kyungsoo
-
p. 15973 - 15991
(2021/07/26)
-
- Ground-State Electron Transfer as an Initiation Mechanism for Biocatalytic C-C Bond Forming Reactions
-
The development of non-natural reaction mechanisms is an attractive strategy for expanding the synthetic capabilities of substrate promiscuous enzymes. Here, we report an "ene"-reductase catalyzed asymmetric hydroalkylation of olefins using α-bromoketones as radical precursors. Radical initiation occurs via ground-state electron transfer from the flavin cofactor located within the enzyme active site, an underrepresented mechanism in flavin biocatalysis. Four rounds of site saturation mutagenesis were used to access a variant of the "ene"-reductase nicotinamide-dependent cyclohexanone reductase (NCR) from Zymomonas mobiles capable of catalyzing a cyclization to furnish β-chiral cyclopentanones with high levels of enantioselectivity. Additionally, wild-type NCR can catalyze intermolecular couplings with precise stereochemical control over the radical termination step. This report highlights the utility for ground-state electron transfers to enable non-natural biocatalytic C-C bond forming reactions.
- Fu, Haigen,Lam, Heather,Emmanuel, Megan A.,Kim, Ji Hye,Sandoval, Braddock A.,Hyster, Todd K.
-
supporting information
p. 9622 - 9629
(2021/07/01)
-
- Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
-
The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
- González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
-
-
- Benzo[d]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selectivelasBquorum sensing inhibitors of Gram-negative bacteria
-
Quorum sensing is a well-known term for describing bacterial cell-cell communication. Bacteria use quorum sensing pathways to respond to external factors such as nutrient availability, defense mechanisms, and coordinate host toxic behaviors such as biofilm formation, virulence production, and other pathogenesis. Discovery of novel compounds which inhibit quorum sensing without being antibiotic are currently emerging fields. Herein, the library of fifteen benzo[d]thiazole/quinoline-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl compounds was designed, synthesized and evaluated to find novel quorum sensing inhibitors. Firstly, compounds were evaluated for their growth inhibitory activities at high concentrations up to 1000 μg mL?1towardPseudomonas aeruginosa. Under our conditions, twelve compounds showed moderate growth inhibitory activities in the concentration tested. To our delight, three compounds3,6and7do not affect the growth of the bacteria which were chosen for the evaluation of quorum sensing inhibitor activities. In theLasBsystem, our compounds3,6,7showed promising quorum-sensing inhibitors with IC50of 115.2 μg mL?1, 182.2 μg mL?1and 45.5 μg mL?1, respectively. In thePqsRsystem, no activity observed suggesting that the selectivity of the compound toward theLasBsystem. In addition,7showed the moderate anti-biofilm formation ofPseudomonas aeruginosa. Docking studies revealed that3,6and7binding to the active site ofPseudomonas aeruginosaquorum sensingLasRsystem with better affinity compared to reference compounds4-NPO. Finally, computation calculations suggest that compounds are a good template for further drug development.
- Quoc, Thang Nguyen,Thanh, Tung Truong,Xuan, Huy Luong
-
p. 28797 - 28808
(2021/09/22)
-
- Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors
-
A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC50 values in the range of 6.31 to 49.89?μM compared to standard drug acarbose (IC50 = 750.0 ± 10.0?μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.
- Alamir, Amir,Asgari, Mohammad Sadegh,Bandarian, Fatemeh,Faramarzi, Mohammad Ali,Hajimiri, Mir Hamed,Hamedifar, Haleh,Hosseini, Samanesadat,Iraji, Aida,Larijani, Bagher,Mahdavi, Mohammad,Mojtabavi, Somayeh,Moradi, Shahram,Nasli Esfahani, Anita,Nasli-Esfahani, Ensieh
-
-
- Acridine Orange Hemi(Zinc Chloride) Salt as a Lewis Acid-Photoredox Hybrid Catalyst for the Generation of α-Carbonyl Radicals
-
A readily accessible organic-inorganic hybrid catalyst is reported for the reductive fragmentation of α-halocarbonyl compounds. The robust hybrid catalyst is a self-stabilizing combination of ZnCl2 Lewis acid and acridine orange as the photoactive organic dye. Mechanistic specifics of this hybrid catalyst have been studied in detail using both photophysical and electrochemical experiments. A systematic study enabled the discovery of the appropriate Lewis acid for the effective LUMO stabilization of α-halocarbonyl compounds and thereby lowering of reduction potential within the range of a standard organic dye. This strategy resolves the issues like dehalogenative hydrogenation or homo-coupling of alkyl radicals by guiding the photoredox cycle through an oxidative quenching pathway. The cooperativity between the photoactive organic dye and the Lewis acid counterparts empowers functionalization with a wide range of coupling partners through efficient and controlled generation of alkyl radicals and serves as an appropriate alternative to the expensive late transition metal-based photocatalysts. To demonstrate the application potential of this cooperative catalytic system, four different synthetic transformations of α-carbonyl bromides were explored with broad substrate scopes.
- Das, Sanju,De Sarkar, Suman,Mandal, Tanumoy
-
supporting information
(2021/12/10)
-
- Microwave-assisted synthesis and luminescent activity of imidazo[1,2-a]pyridine derivatives
-
In this work, a series of phenacyl bromide derivatives was synthesized and employed as key intermediate for the synthesis of substituted imidazo[1,2-a]pyridines. First, phenacyl bromide molecules were obtained from the bromination reaction of acetophenones assisted by microwave irradiation, obtaining the products 4a-v in a 15 minutes reaction with yields in the range of 50% to 99%. Subsequently, the conjugation of these molecules with 2-aminopyridine conduced to the production of imidazo[1,2-a]pyridine derivatives (7a-v) in a 60-second reaction with yields of 24% to 99%. Improved yields were determined with respect to those obtained with more tedious methodologies like thermally and mechanically assisted routes. Intense luminescence emissions in the purple and blue regions of the electromagnetic spectra were observed under UV excitation according to the nature of the substituents. This environmentally friendly methodology is expected to constitute an important class of organic compounds for the development of biomarkers, photochemical sensors, and medicinal applications.
- Rodríguez, Juan C.,Maldonado, Rony A.,Ramírez-García, Gonzalo,Díaz Cervantes, Erik,de la Cruz, Fabiola N.
-
p. 2279 - 2287
(2020/03/16)
-
- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
-
(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
-
supporting information
p. 26 - 35
(2020/01/03)
-
- In(OTf)3-catalyzed intramolecular hydroarylation of α-phenylallyl β-ketosulfones - synthesis of sulfonyl 1-benzosuberones and 1-tetralones
-
In(OTf)3-catalyzed intramolecular hydroarylation of α-phenylallyl β-ketosulfones provides sulfonyl 1-benzosuberones and 1-tetralones in moderate to good yields in refluxing (CH2Cl)2under open-vessel and easy-operation reaction conditions. A plausible mechanism is proposed and discussed. This highly regioselective protocol provides an atom-economic ring-closure route.
- Chang, Meng-Yang,Chang, Yu-Lun,Lai, Kai-Xiang
-
p. 18231 - 18244
(2020/06/08)
-
- Microwave-Assisted multicomponent synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives
-
We present an efficient one-pot, three component microwave-assisted synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives starting from benzo[f]quinoline, 2-bromo-acetophenones or 2-chloro-(N-phenyl)acetamides and electron-deficient alkynes. This synthetic strategy provides a direct and easy access to a range of novel benzo[f]pyrrolo[1,2-a]quinoline derivatives. The method has the advantages of considerable shorter reaction time, reduced solvent consumption, operational simplicity and minimal impact on the environment. Nine new benzo[f]pyrrolo[1,2-a]quinoline derivatives have been synthesized with the new method and they are fully characterized.
- Deleanu, Calin,Draghici, Constantin,Dumitrascu, Florea,Georgescu, Emilian,Georgescu, Florentina,Marinescu, Daniela,Nicolescu, Alina
-
-
- Nickel-Catalyzed Asymmetric Addition of Aromatic Halides to Ketones: Highly Enantioselective Synthesis of Chiral 2,3-Dihydrobenzofurans Containing a Tertiary Alcohol
-
A highly enantioselective and straightforward synthetic procedure to chiral 3-hydroxy-2,3-dihydrobenzofurans has been developed by nickel/bisoxazoline-catalyzed intramolecular asymmetric addition of aryl halides to unactivated ketones, giving 2,3-dihydrobenzofurans with a chiral tertiary alcohol at the C-3 position in good yields and excellent enantioselectivities (up to 92percent yield and 98percent ee). The gram-scale reaction also proceeded smoothly without a loss of yield and enantioselectivity.
- Li, Ying,Li, Wendian,Tian, Jiangyan,Huang, Guozheng,Lv, Hui
-
supporting information
p. 5353 - 5357
(2020/07/14)
-
- Novel benzimidazole derivatives: Cytotoxic and apoptotic properties on lung cancer cell line
-
Background: Benzimidazole derivatives are privileged molecules known to have a wide variety of biological activities. In medicinal chemistry, due to the ring’s structural similarity to nu-cleotides, its derivatives were investigated as new chemotherapeutic agents. Our research group have been studying 1,2-disubstituted benzimidazoles, including thiocarbamoyl group and their potential anticancer activity. Based on previous findings, we synthesized novel 1-[2-(4-substituted phenyl-2-oxoethyl)]-2-[(2/3/4-substituted phenylpiperidin-1-yl)thiocarbamoyl]benzimidazole derivatives (3a-o). Methods: The obtained fifteen derivatives were studied on A549 adenocarcinomic human alveolar basal epithelial cell line and mouse L929 fibroblastic cell line to determine their cytotoxic activity. These compounds were also investigated to identify their apoptotic properties. Results and Discussion: The structures of the compounds based on three different groups differ from each other with the phenyl substituents bonded to the piperazine ring. All of the compounds showed remarkable antitumor activity, but the first five compounds bearing non-substituted phenyl moiety exhibited selective cytotoxicity when compared in terms of potencies to the normal cell line. Conclusion: Compounds 3j, 3m and 3n were identified as the most apoptotic derivatives; however, compounds 3e and 3h provoked apoptosis with the percentages of 10.6 and 10.9% and selective cy-totoxicity.
- Yurtta?, Leyla,?ift?i, Gül?en Akalin,Aksoy, Mehmet Onur,Demirayak, ?eref
-
p. 1227 - 1236
(2020/10/06)
-
- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
-
Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
-
-
- Design and synthesis of new donepezil analogs derived from arylpiperazine scaffold as acetylcholinesterase inhibitors
-
Newly synthesized 4-substituted phenyl-2-(4-substituted phenylpiperazine-1-yl)thiazole derivatives (4a–v) were evaluated in terms of their acetylcholinesterase (AChE) inhibition activities. Twenty-two compounds were tested against AChE at six different concentrations that varied between 10?4 and 10?9 M. The concentrations that inhibited AChE were calculated between 1.15 and 3.45 μM in seven compounds (4a, 4b, 4h, 4l, 4m, 4q, 4r). Compounds 4m, 4b, and 4l represented 1.15, 1.31, 1.34 μM (IC50) inhibitions, respectively. Although the inhibition values are lower than that of donepezil, they are considerable. Modeling studies of these analogs revealed similar positioning with donepezil, in which Ar–Ar interactions with Tyr337 and Trp 286 exist.
- Sahin, Zafer,Biltekin, Sevde Nur,Bülbül, Emre Fatih,Yurttas, Leyla,Berk, Barkin,Demirayak, ?eref
-
p. 283 - 293
(2020/10/29)
-
- Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A1 and/or A2A receptor antagonists
-
A series of fourteen methoxy substituted 2-benzoyl-1-benzofuran derivatives were synthesised and their affinities determined for adenosine A1 and A2A receptors via radioligand binding assays to establish the structure activity relationships pertinent for A1 and A2A affinity. Compound 3j (6,7-dimethoxybenzofuran-2-yl)(3-methoxyphenyl)methanone exhibited A1 affinity (A1Ki (rat) = 6.880 μM) as well as A2A affinity (A2AKi (rat) = 0.5161 μM). Compounds 3a–b & 3i–k exhibited selective affinity towards A1 with Ki values below 10 μM. The results indicate that C6,7-diOCH3 substitution on ring A in combination with meta (C3′)–OCH3 substitution on ring B is beneficial for A1 and A2A affinity and activity. Compounds 3a–b & 3j–k showed low cytotoxicity. Upon in vitro and in silico evaluation, compound 3j may be considered lead-like (i.e. a molecular entity suitable for optimization) and, thus, of value in the design of novel, potent and selective adenosine A1 and A2A receptor antagonists.
- Aucamp, Janine,Janse van Rensburg, Helena D.,Legoabe, Lesetja J.,Terre'Blanche, Gisella
-
-
- FNEW ACTIVATORS OF SIRT1 ENZYME FOR THE TREATMENT OF CARDIOVASCULAR AND CARDIOMETABOLIC PATHOLOGIES
-
This invention describes a class of compounds able to activate the human SIRT1 enzyme and regulate many metabolic functions. This invention relates to compounds that can be employed in medical applications, specifically for the treatment or prevention of cardiometabolic diseases, such as diabetes, and of cardiovascular disorders, such as coronaropathy, heart failure and atherosclerosis.
- -
-
Page/Page column 15; 22
(2019/09/12)
-
- Palladium-Catalyzed Decarboxylative Alkynylation of α-Acyloxyketones by C(sp3)?O Bond Cleavage
-
Palladium-catalyzed decarboxylative alkynylation of α-acyloxyketones triggered by C(sp3)?O bond cleavage is disclosed. The decarboxylation strategy featuring a neutral reaction condition enabled an unprecedent catalytic alkynylation of a ketone enolate. The reaction was applied to a variety of substrates, giving desired products in good yields. We successfully obtained X-ray crystallography of a new palladium–enolate intermediate that was synthesized by a reaction of [Pd(cod)(CH2TMS)2] with XPhos and α-acyloxyketone at room temperature, indicating facile C(sp3)?O bond disconnection.
- Doi, Ryohei,Yabuta, Akimasa,Sato, Yoshihiro
-
supporting information
p. 5884 - 5888
(2019/04/08)
-
- 2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action
-
Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2-yl)amino)benzoic acid (27), showing a submicromolar potency against purified CK2α (IC50 = 0.6 μM). Furthermore, 27 induced apoptosis and cell death in 786-O renal cell carcinoma cells (EC50 = 5 μM) and inhibited STAT3 activation even more potently than the ATP-competitive drug candidate CX-4945 (EC50 of 1.6 μM vs 5.3 μM). Notably, the potencies of our allosteric ligands to inhibit CK2 varied depending on the individual substrate. Altogether, the novel allosteric pocket was proved a druggable site, offering an excellent perspective to develop efficient and selective allosteric CK2 inhibitors.
- Bestgen, Beno?t,Kufareva, Irina,Seetoh, Weiguang,Abell, Chris,Hartmann, Rolf W.,Abagyan, Ruben,Le Borgne, Marc,Filhol, Odile,Cochet, Claude,Lomberget, Thierry,Engel, Matthias
-
p. 1817 - 1836
(2019/02/26)
-
- A visible-light-induced cascade reaction of etherification/C-C cyclization: Efficient synthesis of dibenzo[: B, d] oxepin-7(6 H)-ones
-
A visible-light-induced palladium-catalyzed cascade reaction was developed by etherification/C-C coupling cyclization of α-bromoacetophenones with phenols. A series of dibenzo[b,d]oxepin-7(6H)-one derivatives were efficiently synthesized by using this method in good yields. Furthermore, this method was applied to the synthesis of protosappanin A. The protocol has advantages such as simple reaction conditions, wide range of substrates and high reaction efficiency.
- Fu, Wanyong,Yu, Aixia,Jiang, Hongshuo,Zuo, Minghui,Wu, Hongfeng,Yang, Zhongwen,An, Qi,Sun, Zhizhong,Chu, Wenyi
-
supporting information
p. 3324 - 3327
(2019/04/03)
-
- Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL
-
Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in physiology and pathology. However, only limited ‘reader’ probes have been developed, which restricted our understanding towards these macromolecules and their roles in cells or animals. Here, we reported a structure-guided approach to develop and characterize benzo [d]oxazol-2(3H)-one analogs as the first potent and selective small-molecule inhibitors of chromodomain Y-like (CDYL), a histone methyllysine reader protein. The binding conformation between the chromodomain of CDYL and the modified peptidomimetics was studied via molecular docking and dynamic simulations, facilitating subsequent virtual screening of tens of hits from Specs chemical library validated by SPR technique (KD values: from 271.1 μM to 5.4 μM). Further design and synthesis of 43 compounds helped to interpret the structure-activity relationship (SAR) that lead to the discovery of novel small-molecule inhibitors of CDYL. Compound D03 (KD: 0.5 μM) was discovered and showed excellent selectivity among other chromodomain proteins, including CDYL2 (>140 folds), CDY1 (no observed binding) and CBX7 (>32 folds). Moreover, we demonstrated that D03 engaged with endogenous CDYL in a dose-dependent manner, and perturbed the recruitment of CDYL onto chromatin, resulting in transcriptional derepression of its target genes. Finally, the results showed that D03 promoted the development and branching of neurodendrites by inhibiting CDYL in hippocampal and cortical cultured neurons. This study not only discovers the first selective small-molecule inhibitors of CDYL, but provids a new chemical tool to intervene the dynamic nature of bio-macromolecules involved in epigenetic mechanism.
- Yang, Lixin,Liu, Yongqing,Fan, Minghua,Zhu, Guiwang,Jin, Hongwei,Liang, Jing,Liu, Zhenming,Huang, Zhuo,Zhang, Liangren
-
-
- Vinylethylene Carbonates as α,β-Unsaturated Aldehyde Surrogates for Regioselective [3 + 3] Cycloaddition
-
Herein, we report a novel stepwise addition-controlled ring size method, to access tetrahydropyrimidines through an operationally simple [3 + 3] cycloaddition of vinylethylene carbonates with triazinanes. Interestingly, we could also use this method for a [3 + 3] oxidative cycloaddition, which allows the facile synthesis of polysubstituted terphenyls under mild conditions. Mechanistic studies suggest that vinylethylene carbonates could generate α,β-unsaturated aldehydes as 3-carbon synthons for cycloaddition via a combination process of Pd-catalyzed decarboxylation and β-H elimination.
- Xu, Yi,Chen, Lu,Yang, Yu-Wen,Zhang, Zhiqiang,Yang, Weibo
-
supporting information
p. 6674 - 6678
(2019/09/03)
-
- Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors
-
Dementia is a cognitive disorder mostly associated with Alzheimer's disease (AD) in addition to being seen in many other diseases of the central nervous system (CNS). The limited number of drugs is not sufficient to provide adequate improvement to increase the quality of life of patients suffering from this symptom; therefore, all treatment options should be evaluated in detail. In this study, new molecules, [2-(4-(2/3/4-substituted phenyl)piperazin-1-yl)-4-phenylthiazol-5-yl][3/4-substituted phenyl]methanone derivatives (1-44), were obtained and analyzed in terms of their anticholinesterase activities. Kinetic mode and molecular interactions were also evaluated. An enzyme inhibition study was undertaken on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the Ellman method. Maestro program was used in molecular modeling studies. Forty-four compounds were evaluated on AChE and BChE enzymes at 10?3 and 10?4 concentrations. The inhibition concentrations were calculated as 0.268μM to 2.104μM for six compounds (4, 5, 16, 27, 37, and 38) on AChE. Compound 5 including the 4-methoxy substituent (IC50: 0.268μM) and compound 38 containing the 4-methoxy and 3-methyl substituents (IC50: 0.286μM) showed the highest AChE inhibitory activity. They were further examined in terms of hydrogen bonding with Arg296 and Ar-Ar interaction with Trp286. The activity of compound 5 was also assessed in mixed-type kinetic mode.
- Demirayak, ?eref,?ahin, Zafer,Erta?, Merve,Bülbül, Emre Fatih,Bender, Ceysu,Biltekin, Sevde Nur,Berk, Barkin,Sa?l?k, Begüm Nurpelin,Levent, Serkan,Yurtta?, Leyla
-
p. 3370 - 3386
(2019/11/03)
-
- LEGO-Inspired Drug Design: Unveiling a Class of Benzo[d]thiazoles Containing a 3,4-Dihydroxyphenyl Moiety as Plasma Membrane H+-ATPase Inhibitors
-
The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure–activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for the design, synthesis, and discovery of benzo[d]thiazoles containing a 3,4-dihydroxyphenyl moiety as potential Pma1p inhibitors. A series of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 μm in an in vitro plasma membrane H+-ATPase assay. These compounds were also found to strongly inhibit the action of proton pumping when Pma1p was reconstituted into liposomes. 1-(3,4-Dihydroxyphenyl)-2-((6-(trifluoromethyl)benzo[d]thiazol-2-yl)thio)ethan-1-one (compound 38) showed inhibitory activities on the growth of Candida albicans and Saccharomyces cerevisiae, which could be correlated and substantiated with the ability to inhibit Pma1p in vitro.
- Tung, Truong-Thanh,Dao, Trong T.,Junyent, Marta G.,Palmgren, Michael,Günther-Pomorski, Thomas,Fuglsang, Anja T.,Christensen, S?ren B.,Nielsen, John
-
-
- Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives
-
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.
- Sahin, Zafer,Ertas, Merve,Berk, Bark?n,Biltekin, Sevde Nur,Yurttas, Leyla,Demirayak, Seref
-
p. 1986 - 1995
(2018/03/12)
-
- One-Pot Sequential Bromination and Fluorination to Access 3-Fluoroimidazo[1,2-a]pyridines from Arylketones
-
3-Fluoro-2-arylimidazo[1,2-a]pyridines were selectively synthesised in one-pot from acetophenones and 2-aminopyridines under mild conditions. The sequence of reactions involved bromination, condensation, and late-stage fluorination. Two halogenating reagents play key roles in the process. We found that tetrabutylammonium tribromide and SelectfluorTM gave excellent yields of the desired products in the one-pot sequential reaction.
- Udavant, Rohini N.,Yadav, Ashok R.,Shinde, Sandip S.
-
p. 3432 - 3436
(2018/07/25)
-
- Divergent synthesis of N-heterocycles by Pd-catalyzed controllable cyclization of vinylethylene carbonates
-
Here, we report a palladium-catalyzed controllable cyclization of vinyl ethylene carbonates that proceeds through formal migration [2+3] and [5+2] cycloadditions, respectively, under mild conditions. The transformation described here affords a series of synthetically versatile 5,7-membered N-heterocycles which are found in natural products and pharmaceuticals with biological and medicinal properties.
- Yang, Yuwen,Yang, Weibo
-
supporting information
p. 12182 - 12185
(2018/11/21)
-
- Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C?N/C?S Bond Formation in Allylic Surrogates
-
Switchable catalytic transformation of reactants can be a powerful approach towards diversity-orientated synthesis from easily available molecular synthons. Herein, an endogenous ligand-controlled, Pd-catalyzed allylic substitution allowing for either selective C?N or C?S bond formation using vinylethylene carbonates (VECs) and N-sulfonylhydrazones as coupling partners has been developed. This versatile methodology provides a facile, divergent route for the highly chemo- and stereoselective synthesis of functional allylic sulfones or sulfonohydrazides. The newly developed protocol features wide substrate scope (nearly 80 examples), broad functional group tolerance, and potential for the late-stage functionalization of bioactive compounds. The isolation and crystallographic analysis of a catalytically competent π-allyl Pd complex suggests that the pathway leading to the allylic products proceeds through a different manifold as previously proposed for the functionalization of VECs with nucleophiles.
- Deng, Lei,Kleij, Arjan W.,Yang, Weibo
-
supporting information
p. 19156 - 19161
(2018/11/30)
-
- Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
-
(Table presented.). After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs. In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N′-benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%–83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.
- Sahin, Zafer,Ertas, Merve,Bender, Ceysu,Bülbül, Emre F.,Berk, Barkin,Biltekin, Sevde N.,Yurtta?, Leyla,Demirayak, ?eref
-
p. 406 - 425
(2018/10/26)
-
- Functionalized N-containing heterocyclic scaffolds derived from N-substituted pyrroles via inter- and intramolecular annulations
-
Two series of N-containing heterocycles were synthesized by one-step intramolecular or intermolecular annulations of N-substituted pyrrole-2-carbaldehydes and pyrrole-2-carbonitriles. These facile and atom-economic synthetic routes involved the inherent three potential electrophilic and nucleophilic reactive sites of the synthons and the reaction solvent plays a crucial role leading to these different types of products. Additionally, plausible mechanisms are proposed.
- Shao, Nana,Li, Jinbiao,Zhu, Huajian,Zhang, Shuaizhong,Zou, Hongbin
-
supporting information
p. 6088 - 6094
(2018/09/17)
-
- Structure-Based Design and Discovery of New M2 Receptor Agonists
-
Muscarinic receptor agonists are characterized by apparently strict restraints on their tertiary or quaternary amine and their distance to an ester or related center. On the basis of the active state crystal structure of the muscarinic M2 receptor in complex with iperoxo, we explored potential agonists that lacked the highly conserved functionalities of previously known ligands. Using structure-guided pharmacophore design followed by docking, we found two agonists (compounds 3 and 17), out of 19 docked and synthesized compounds, that fit the receptor well and were predicted to form a hydrogen-bond conserved among known agonists. Structural optimization led to compound 28, which was 4-fold more potent than its parent 3. Fortified by the discovery of this new scaffold, we sought a broader range of chemotypes by docking 2.2 million fragments, which revealed another three micromolar agonists unrelated either to 28 or known muscarinics. Even pockets as tightly defined and as deeply studied as that of the muscarinic reveal opportunities for the structure-based design and the discovery of new chemotypes.
- Fish, Inbar,St??el, Anne,Eitel, Katrin,Valant, Celine,Albold, Sabine,Huebner, Harald,M?ller, Dorothee,Clark, Mary J.,Sunahara, Roger K.,Christopoulos, Arthur,Shoichet, Brian K.,Gmeiner, Peter
-
supporting information
p. 9239 - 9250
(2017/11/30)
-
- Visible Light as a Sole Requirement for Intramolecular C(sp3)-H Imination
-
A novel, simple, and practical visible-light-mediated intramolecular α-C(sp3)-H imination of tertiary aliphatic amines containing β-O-aryl oximes leading to N-heterocycles has been developed. The reaction was performed well at rt with tolerance of some functional groups. Importantly, the selective C-H functionalization did not require added catalyst, oxidant, additive, acid, and base; visible light was the sole requirement.
- Li, Jingjing,Zhang, Pengxiang,Jiang, Min,Yang, Haijun,Zhao, Yufen,Fu, Hua
-
supporting information
p. 1994 - 1997
(2017/04/28)
-
- Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3β inhibitors
-
We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3β inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3β inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3β. Based on docking studies, new hydrogen bonding between the nitrogen atom of the piperazine moiety and the oxygen atom of the main chain of Gln185 has been indicated, which may contribute to increased activity compared with that of the corresponding phenylmorpholine analogues. Effect of the stereochemistry of the phenylpiperazine moiety is also discussed.
- Usui, Yoshihiro,Uehara, Fumiaki,Hiki, Shinsuke,Watanabe, Kazutoshi,Tanaka, Hiroshi,Shouda, Aya,Yokoshima, Satoshi,Aritomo, Keiichi,Adachi, Takashi,Fukunaga, Kenji,Sunada, Shinji,Nabeno, Mika,Saito, Ken-Ichi,Eguchi, Jun-ichi,Yamagami, Keiji,Asano, Shouichi,Tanaka, Shinji,Yuki, Satoshi,Yoshii, Narihiko,Fujimura, Masatake,Horikawa, Takashi
-
p. 3726 - 3732
(2017/07/27)
-
- Citric Acid-catalyzed Synthesis of 2,4-Disubstituted Thiazoles from Ketones via C–Br, C–S, and C–N Bond Formations in One Pot: A Green Approach
-
An improved and greener protocol has been developed for the synthesis of 2,4-disubstituted thiazoles via C–Br, C–S, and, C–N bond formations in a single step from readily available ketones, N-bromosuccinimide (NBS), and thiourea catalyzed by citric acid in a mixture of ethanol and water (3:1) under reflux conditions. This method has the advantages of freedom from the isolation of lachrymatory α-bromoketones, ease of carrying out, cleaner reaction profile, broad substrate scope, freedom from chromatographic purification, and suitability for large-scale synthesis.
- Gundala, Trivikram Reddy,Godugu, Kumar,Nallagondu, Chinna Gangi Reddy
-
p. 1408 - 1416
(2017/10/23)
-
- Preparation method of 2-bromo-3'-methoxyacotophenone
-
The invention relates to a preparation method of a medical intermediate, in particular to a preparation method of 2-bromo-3'-methoxyacotophenone. According to the preparation method, the target product is prepared by taking acetophenone, dimethyl sulfate and a brominating agent as main raw materials through the steps of a nitration reaction, a reduction reaction, a diazotization reaction, a hydrolysis reaction, a methylation reaction, a bromination reaction and the like. The preparation method has the advantages that the yields of the reactions are all 80% or above, the purity of the obtained target product 2-bromo-3'-methoxyacotophenone can reach 99.2%, the cost is low, and the yield and the purity are high; in the preparation process, the reaction conditions are mild, operation is easy, little harm is generated to the environment, and the preparation method is suitable for large-scale production.
- -
-
-
- Ammonium hydrotribromide salts as convenient and selective brominating agents of aryl methyl ketones
-
A simple and improved protocol for the α-monobromination of acetophenone and acetyl carbazole derivatives using different ammonium hydrotribromide salts under mild reaction condition was described.
- Badali, Mohammad,Khalafy, Jabbar,Alidoost, Elnaz,Aghazadeh, Masomeh
-
p. 859 - 863
(2016/11/21)
-
- Aq HBr–NaNO2–KI/air: a new catalytic system for α-monobromination of ketones
-
An efficient approach for α-bromination of aryl alkyl ketones, utilizing a system consisting of aqueous hydrobromic acid as bromine source, sodium nitrite–KI as catalyst, and air as terminal oxidant, has been developed. The method offers advantages of selective monobromination, mild reaction conditions, broad substrate scope, and good yield. The use of air as the terminal oxidant makes the reaction very attractive from both economical and environmental viewpoints.
- Ghorpade, Archana K.,Huddar, Sameerana N.,Akamanchi, Krishnacharya G.
-
supporting information
p. 4918 - 4921
(2016/10/22)
-
- 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation
-
In our endeavor towards the development of effective VEGFR-2 inhibitors, three novel series of phthalazine derivatives based on 1-piperazinyl-4-arylphthalazine scaffold were synthesized. All the newly prepared phthalazines 16a-k, 18a-e and 21a-g were evaluated in vitro for their inhibitory activity against VEGFR-2. In particular, compounds 16k and 21d potently inhibited VEGFR-2 at sub-micromolar IC50 values 0.35 ± 0.03 and 0.40 ± 0.04 μM, respectively. Moreover, seventeen selected compounds 16c-e, 16g, 16h, 16j, 16k, 18c-e and 21a-g were evaluated for their in vitro anticancer activity according to US-NCI protocol, where compounds 16k and 21d proved to be the most potent anticancer agents. While, compound 16k exhibited potent broad spectrum anticancer activity with full panel GI50 (MG-MID) value of 3.62 μM, compound 21d showed high selectivity toward leukemia and prostate cancer subpanels [subpanel GI50 (MG-MID) 3.51 and 5.15 μM, respectively]. Molecular docking of compounds16k and 21d into VEGFR-2 active site was performed to explore their potential binding mode.
- Abou-Seri, Sahar M.,Eldehna, Wagdy M.,Ali, Mamdouh M.,Abou El Ella, Dalal A.
-
p. 165 - 179
(2015/11/25)
-
- Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
-
The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
- Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
-
p. 1166 - 1173
(2016/07/27)
-
- Identification of novel 2-aminothiazole conjugated nitrofuran as antitubercular and antibacterial agents
-
The emergence of antibiotic resistant pathogens is an ongoing main problem in the therapy of bacterial infections. In order to develop promising antitubercular and antibacterial lead compounds, we designed and synthesized a new series of derivatives of 2-aminothiazole conjugated nitrofuran with activities against both Mycobacterium tuberculosis and Staphylococcus aureus. Eight compounds 12e, 12k, 12l, 12m, 18a, 18d, 18e, and 18j emerged as promising antitubercular agents. Structure–activity relationships (SARs) were discussed and showed that the derivatives substituted at the position-3 of benzene of 5-nitro-N-(4-phenylthiazol-2-yl)furan-2-carboxamide exhibited superior potency. The most potent compound 18e, substituted with benzamide at this position, displayed minimum inhibitory concentrations (MICs) of 0.27 μg/mL against Mtb H37Ra and 1.36 μg/mL against S. aureus. Furthermore, compound 18e had no obvious cytotoxicity to normal Vero cells (IC50= 50.2 μM). The results suggest that the novel scaffolds of aminothiazole conjugated nitrofuran would be a promising class of potent antitubercular and antimicrobial agents.
- Ran, Kai,Gao, Chao,Deng, Hongxia,Lei, Qian,You, Xinyu,Wang, Ningyu,Shi, Yaojie,Liu, Zhihao,Wei, Wei,Peng, Cuiting,Xiong, Lu,Xiao, Kunjie,Yu, Luoting
-
supporting information
p. 3669 - 3674
(2016/07/21)
-
- Palladium-Catalyzed Chemo- and Enantioselective C?O Bond Cleavage of α-Acyloxy Ketones by Hydrogenolysis
-
A chemoselective C?O bond cleavage of the ester alkyl side-chain of α-acyloxy ketones was realized for the first time by a highly efficient palladium-catalyzed hydrogenolysis (S/C=6000, the highest catalytic efficiency by far). Furthermore, a kinetic resolution of α-acyloxy ketones was first developed by enantioselective hydrogenolysis with good yields and up to 99 % ee.
- Chen, Jianzhong,Zhang, Zhenfeng,Liu, Delong,Zhang, Wanbin
-
supporting information
p. 8444 - 8447
(2016/07/19)
-
- A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines
-
A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines has been successfully realized with 2.5 mol% of B(C6F5)3 as a catalyst to furnish a variety of 3,4-dihydro-2H-1,4-benzoxazines in 93-99% yields. Up to 42% ee was also achieved for the asymmetric hydrogenation with the use of a chiral diene and HB(C6F5)2.
- Wei, Simin,Feng, Xiangqing,Du, Haifeng
-
supporting information
p. 8026 - 8029
(2016/09/09)
-
- Method for preparing 3,4-dihydrobenzo[b][1,4]oxazine derivatives
-
The invention provides a method for preparing 3,4-dihydrobenzo[b][1,4]oxazine derivatives. The method comprises the following step: carrying out reduction reaction on [b][1,4]oxazines in the presence of hydrogen gas by using B(C6F5)3 as a catalyst to obtain the mixture containing the 3,4-dihydrobenzo[b][1,4]oxazines disclosed as Formula I. Benzo[b][1,4]oxazines in different structures are used as a substrate to synthesize the benzo[b][1,4]oxazines at high yield by using the B(C6F5)3 as the catalyst. The method has the advantages of cheap and accessible raw materials, high reaction activity, no participation of transition metals and wide substrate application range, and has huge industrialization potential.
- -
-
Paragraph 0060
(2016/10/10)
-
- Synthesis and biological evaluation of novel C1-glycosyl thiazole derivatives as acetylcholinesterase inhibitors
-
A new series of C1-glycosyl thiazole derivatives was synthesised by the reaction of 1-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea with 2-bromoacetophenone derivatives. Subsequent removal of the acetyl groups were conducted using NaOMe-MeOH. The structures of all new products were confirmed by IR, 1H NMR and HRMS (ESI). The acetylcholinesterase inhibitory activities of these new compounds were tested. Among them, N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(4-nitrophenyl)-1,3-thiazole-2-amine showed the best activity with an inhibition rate of 43.21%.
- Yin, Long,Cheng, Feng-Chang,Li, Qu-Xiang,Liu, Wei-Wei,Liu, Xiu-Jian,Cao, Zhi-Ling,Shi, Da-Hua
-
p. 545 - 548
(2016/10/05)
-
- Synthesis and characterization of novel oxime derivatives
-
Background: The synthesis of effective drugs are very important for the scientist. The various biological effects of the thiazole, oxime and ether functional groups are well known properties by the drug developers. So we have synthesised new molecules which contains three of them on the same molecules. Methods: The acetophenone derivatives have been used for synthesis new oximes. The synthetic pathway includes mainly four steps. s1. α-Bromination of acetophenone derivatives, s2. Synthesis of thiazole ring using brominated acetophenones, s3. Synthesis of ethers using synthesised thiazole, s4. Synthesis of oximes. Results: The synthesised molecules characterised using IR,1H-NMR, 13C-NMR and elementel analysis methods. Conclusion: The new oximes which include thiazole and ether groups have been synthesised using acetophenone derivatives.
- Arslan, Taner,Keskin, Serhat,Demirayak, Seref
-
p. 672 - 677
(2017/01/13)
-