- No-carrier-added labeling of the neuroprotective Ebselen with selenium-73 and selenium-75
-
Selenium-73 is a positron emitting non-standard radionuclide, which is suitable for positron emission tomography. A copper-catalyzed reaction allowed no-carrier-added labeling of the anti-inflammatory seleno-organic compound Ebselen with 73Se and 75Se under addition of sulfur carrier in a one-step reaction. The new authentically labeled radioselenium molecule is thus available for preclinical evaluation and positron emission tomography studies.
- Helfer, Andreas,Ermert, Johannes,Humpert, Sven,Coenen, Heinz H.
-
-
Read Online
- Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis
-
Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors
- Cao, Hongxuan,Chen, Han,Han, Xinya,Huang, Yunyuan,Liu, Jiaqi,Peng, Chao,Rao, Li,Ren, Yanliang,Sheng, Chunquan,Su, Chen,Tu, Jie,Wan, Chen,Wan, Jian,Wen, Wuqiang
-
p. 2656 - 2674
(2022/02/09)
-
- Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease
-
The reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID-19) and other diseases. We report structure-activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of Mpro, particularly with respect to improved selectivity.
- Brewitz, Lennart,Choudhry, Hani,Malla, Tika R.,Salah, Eidarus,Schofield, Christopher J.,Suits, Timothy F.,Thun-Hohenstein, Siegfried T. D.,Tumber, Anthony
-
supporting information
(2021/12/30)
-
- Electrochemical synthesis for benzisothiazol-3(2H)-ones by dehydrogenative N[sbnd]S bond formation
-
Herein, we report an electrochemical method for the synthesis of benzisothiazol-3(2H)-ones from 2-mercaptobenzamides. The electrochemical reaction proceeds through intramolecular N[sbnd]H/S[sbnd]H coupling cyclization reaction by generating H2 as the nonhazardous side product. Moreover, the developed procedure is highly advantageous due to its short reaction time, mild conditions and wide substrate scope without the employment of metal catalyst and exogenous-oxidant.2009 Elsevier Ltd. All rights reserved.
- Chen, Junmin,Sheng, Shouri,Xiong, Zhiqiang,Zhong, Qihao
-
supporting information
(2021/08/26)
-
- High-throughput tandem-microwell assay for ammonia repositions FDA-Approved drugs to inhibit Helicobacter pylori urease
-
To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, that is, panobinostat, dacinostat, ebselen, captan, and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from killing human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.
- Fang, Houqin,Huang, Shengshuo,Li, Fangzheng,Liao, Lujian,Liu, Fan,Liu, Qi,Wu, Fang,Wu, Xin-Yan,Xiao, Zhuping,Xu, Jinyi,Yu, Jing,Zhang, Yan-Xia,Zhou, Yueyang
-
-
- Bioisosteric investigation of ebselen: Synthesis and in vitro characterization of 1,2-benzisothiazol-3(2H)-one derivatives as potent New Delhi metallo-β-lactamase inhibitors
-
Carbapenem-resistant Enterobacteriaceae (CRE) producing New Delhi metallo-β-lactamase (NDM-1) cause untreatable bacterial infections, posing a significant threat to human health. In the present study, by employing the concept of bioisosteric replacement of the selenium moiety of ebselen, we have designed, synthesized and characterized a small compound library of 2-substituted 1,2-benzisothiazol-3(2H)-one derivatives and related compounds for evaluating their cytotoxicity and synergistic activity in combination with meropenem against the E. coli Tg1 (NDM-1) strain. The most promising compound 3a demonstrated potent synergistic activity against a panel of clinically isolated NDM-1 positive CRE strains with FICI as low as 0.09. Moreover, its IC50 value and inhibition mechanism were also confirmed by using the enzyme inhibition assay and the ESI-MS analysis respectively. Importantly, compound 3a has acceptable toxicity and is not a PAINS. Because of its structural simplicity and potent synergistic activity in combination with meropenem, we propose that compound 3a may be a promising meropenem adjuvant and a new series of such compounds may worth further investigations.
- Jin, Wen Bin,Xu, Chen,Cheung, Qipeng,Gao, Wei,Zeng, Ping,Liu, Jun,Chan, Edward W.C.,Leung, Yun-Chung,Chan, Tak Hang,Wong, Kwok-Yin,Chen, Sheng,Chan, Kin-Fai
-
-
- Synthetic method 1-2 - benzisothiazol -3 -one compound (by machine translation)
-
The invention discloses a synthetic method of 1-2 - benzisothiazol -3 -one compound, and belongs to the field of chemical synthesis. 2 - 1-benzisothiazol 2 -one compounds are synthesized through acid chlorination, amidation and cyclization reaction by using the sulfenyl-substituted benzoic acid extracted from BIT process -3 - waste water as a starting raw material. The method disclosed by the invention has the advantages of mild reaction conditions, simple and convenient operation, strong practicability, less waste water, high product purity and the like, and is suitable for large-scale industrial production. The technical scheme provided by the invention is resource utilization and preparation 1 of wastewater extract produced in BIT production, and a feasible method is provided for the 2 -benzisothiazol -3 -one compound. (by machine translation)
- -
-
-
- Novel synthesis method of N-substituted benzisothiazoline-3-ketone derivative
-
The invention discloses a novel synthesis method of an N-substituted benzisothiazoline-3-ketone derivative. The preparation method comprises the following steps: by taking a dithiosalicylic acid derivative and sulfur as raw materials, introducing chlorine or bromine to obtain a halogenated thiobenzoyl halide derivative, then preferably dropwise adding a mixed solution of primary amine and tertiaryamine, and carrying out reaction and ring closing to obtain the N-substituted benzisothiazole-3-ketone. The method disclosed by the invention is simple in process, safe and controllable, and easy forindustrial large-scale production.
- -
-
Paragraph 0053-0055
(2020/07/02)
-
- 1,2-BENZISOSELENAZOL-3(2H)-ONE AND 1,2-BENZISOTHIAZOL-3(2H)-ONE DERIVATIVES AS BETA-LACTAM ANTIBIOTIC ADJUVANTS
-
Provided herein are compositions and methods useful in the treatment of beta-lactam antibiotic resistant bacteria.
- -
-
Paragraph 0282-0285; 0301; 0302
(2019/10/04)
-
- Domino Reactions Initiated by Copper-Catalyzed Aryl-I Bond Thiolation For the Switchable Synthesis of 2,3-Dihydrobenzothiazinones and Benzoisothiazolones
-
The three-component reactions of o-iodobenzamides, elemental sulfur and dichloromethane (DCM) providing 2,3-dihydro-4H-benzo[e][1,3]thiazin-4-ones (2,3-dihydrobenzothiazinones) are accomplished via copper-catalyzed aryl C?I thiolation and subsequent N-, S-hetero ring formation. In addition, the in situ aryl C?I bond thiolation is also employed for the switchable synthesis of benzo[d]isothiazol-3(2H)-ones (benzoisothiazolones) by subjecting o-iodobenzamides, elemental sulfur to the copper-catalyzed condition with microwave irradiation. (Figure presented.).
- Xiong, Jin,Zhong, Guofeng,Liu, Yunyun
-
supporting information
p. 550 - 555
(2018/12/14)
-
- Co-Catalyzed Intramolecular S-N Bond Formation in Water for 1,2-Benzisothiazol-3(2H)-ones and 1,2,4-Thiadiazoles Synthesis
-
An efficient and versatile Co-catalyzed intramolecular S-N bond formation in water to synthesize 1,2-benzisothiazol-3(2H)-one and 1,2,4-thiadiazoles derivatives in good to excellent yields was developed. The transformation showed great tolerance with a broad range of substituents. The mother liquor was able to be recycled 6 times with minor loss in product yield.
- Yang, Liting,Song, Lijuan,Tang, Shanyu,Li, Longjia,Li, Heng,Yuan, Bingxin,Yang, Guanyu
-
p. 1281 - 1285
(2019/01/14)
-
- Ebsulfur as a potent scaffold for inhibition and labelling of New Delhi metallo-β-lactamase-1 in vitro and in vivo
-
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a–b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16–9 μM, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 μM. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 μg/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli EC08 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.
- Su, Jianpeng,Liu, Jiayun,Chen, Cheng,Zhang, Yuejuan,Yang, Kewu
-
supporting information
p. 192 - 201
(2018/12/02)
-
- Method for generating benzisothiazolinone compounds by catalyzing oxidization of molecular oxygen in aqueous phase
-
The invention provides a method for synthesizing benzisothiazolinone compounds by catalyzing oxidization of molecular oxygen in an aqueous phase. A water-soluble transition metal phthalocyanine compound is taken as a catalyst, and a thiosalicylic acid ami
- -
-
Paragraph 0033-0036
(2019/01/16)
-
- Benzisothiazol-3-ones through a Metal-Free Intramolecular N–S Bond Formation
-
The highly efficient synthesis of benzoisothiazol-3-ones from thiobenzamides has been described with good functional group compatibility and excellent yields. This work represents the first example of selectfluor-promoted N–S bond formation processes. This method provides a facile approach to access various important bioactive benzoisothiazol-3-ones.
- Yang, Ke,Zhang, Hao,Niu, Ben,Tang, Tiandi,Ge, Haibo
-
p. 5520 - 5523
(2018/10/26)
-
- Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects
-
Various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had MIC50 of 0.4?μg/mL (cf. Gentamicin?=?0.78?μg/mL). CLogP value, optimally in the range of 2.5–3.5, appeared to contribute more to the activity than the steric and electronic effects of groups attached at nitrogen. By and large, their anti-fungal activities also followed a similar trend with respect to the structure and CLogP values. The best potency of IC50?=?0.1?μg/mL was shown by N-benzyl derivative (1.7) against Aspergillus fumigatus; it was also potent against Candida albicans, Cryptococcus neoformans, Sporothrix schenckii, and Candida parapsilosis with IC50 values ranging from 0.4 to 1.3?μg/mL. Preliminary studies also showed that this class of compounds have the ability to target malaria parasite with IC50 values in low micromolar range, and improvement of selectivity is possible through structure optimization.
- Gopinath,Yadav,Shukla,Srivastava,Puri,Muraleedharan
-
p. 1291 - 1295
(2017/06/19)
-
- Potassium bromide catalyzed N[sbnd]S bond formation via oxidative dehydrogenation
-
N-Substituted benzo[d]isothiazol-3(2H)-ones are a family of compounds with extremely important application. Recently, we have developed a new green pathway to synthesize these compounds via potassium bromide-catalyzed intramolecular oxidative dehydrogenative cyclization. This reaction has high functional group tolerance and affords excellent yield even in gram scale.
- Yu, Tian-Qun,Hou, Yong-Sheng,Jiang, Yi,Xu, Wen-Xuan,Shi, Tao,Wu, Xia,Zhang, Jin-Chao,He, Dian,Wang, Zhen
-
p. 2084 - 2087
(2017/05/10)
-
- REDOX DEHYDRATION COUPLING CATALYSTS AND METHODS RELATED THERETO
-
This disclosure relates to synthetic coupling methods using catalytic molecules. In certain embodiments, the catalytic molecules comprise heterocyclic thiolamide, S-acylthiosalicylamide, disulfide, selenium containing heterocycle, diselenide compound, ditelluride compound or tellurium containing heterocycle. Catalytic molecules disclosed herein are useful as catalysts in the transformation of hydroxy group containing compounds to amides, esters, ketones, and other carbon to heteroatom or carbon to carbon transformations.
- -
-
Page/Page column 60
(2017/08/01)
-
- An efficient approach to construct benzisothiazol-3(2: H)-ones via copper-catalyzed consecutive reaction of 2-halobenzamides and carbon disulfide
-
An efficient copper-catalyzed reaction for the synthesis of benzisothiazol-3(2H)-ones has been developed, starting from easily available 2-halobenzamides and carbon disulfide, which gave the corresponding target products in 30-89% yield for 25 examples. The reaction proceeds via a consecutive process with S-C bond and S-N bond formation.
- Li, Ting,Yang, Lei,Ni, Kaidong,Shi, Zhenyu,Li, Fei,Chen, Dongyin
-
p. 6297 - 6303
(2016/07/11)
-
- Development of ebsulfur analogues as potent antibacterials against methicillin-resistant Staphylococcus aureus
-
Antibiotic resistance is a worldwide problem that needs to be addressed. Staphylococcus aureus is one of the dangerous “ESKAPE” pathogens that rapidly evolve and evade many current FDA-approved antibiotics. Thus, there is an urgent need for new anti-MRSA compounds. Ebselen (also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one) has shown promising activity in clinical trials for cerebral ischemia, bipolar disorder, and noise-induced hearing loss. Recently, there has been a renewed interest in exploring the antibacterial properties of ebselen. In this study, we synthesized an ebselen-inspired library of 33 compounds where the selenium atom has been replaced by sulfur (ebsulfur derivatives) and evaluated them against a panel of drug-sensitive and drug-resistant S. aureus and non-S. aureus strains. Within our library, we identified three outstanding analogues with potent activity against all S. aureus strains tested (MIC values mostly ?2?μg/mL), and numerous additional ones with overall very good to good antibacterial activity (1–7.8?μg/mL). We also characterized the time-kill analysis, anti-biofilm ability, hemolytic activity, mammalian cytotoxicity, membrane-disruption ability, and reactive oxygen species (ROS) production of some of these analogues.
- Ngo, Huy X.,Shrestha, Sanjib K.,Green, Keith D.,Garneau-Tsodikova, Sylvie
-
supporting information
p. S1 - S53
(2016/12/07)
-
- Benzoisothiazolone organo/copper-cocatalyzed redox dehydrative construction of amides and peptides from carboxylic acids using (EtO)3P as the reductant and O2 in air as the terminal oxidant
-
Carboxylic acids and amine/amino acid reactants can be converted to amides and peptides at neutral pH within 5-36 h at 50 °C using catalytic quantities of a redox-active benzoisothiazolone and a copper complex. These catalytic "oxidation-reduction condensation" reactions are carried out open to dry air using O2 as the terminal oxidant and a slight excess of triethyl phosphite as the reductant. Triethyl phosphate is the easily removed byproduct. These simple-to-run catalytic reactions provide practical and economical procedures for the acylative construction of C-N bonds.
- Liebeskind, Lanny S.,Gangireddy, Pavankumar,Lindale, Matthew G.
-
p. 6715 - 6718
(2016/06/14)
-
- Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1
-
We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High-throughput screening (HTS)
- Bravo, Yalda,Teriete, Peter,Dhanya, Raveendra-Panickar,Dahl, Russell,Lee, Pooi San,Kiffer-Moreira, Tina,Ganji, Santhi Reddy,Sergienko, Eduard,Smith, Layton H.,Farquharson, Colin,Millan, Jose Luis,Cosford, Nicholas D.P.
-
p. 4308 - 4311
(2014/09/17)
-
- Benzisothiazolones arrest the cell cycle at the G2/M phase and induce apoptosis in HeLa cells
-
Anticancer activities of a series of benzisothiazolones having alkyl, aryl and aralkyl substituents on the nitrogen atom and the mechanistic basis of cytotoxicity are presented. Cellular responses like DNA laddering, disruption of mitochondrial membrane potential and caspase-3 activation on incubation of HeLa cells with representative compounds from this group suggested the induction of apoptosis through an intrinsic pathway. Their ability to arrest the cell cycle at the G2/M phase was confirmed by flow cytometric analysis.
- Gopinath, Pushparathinam,Ramalingam, Krishnan,Muraleedharan, Kannoth Manheri,Karunagaran, Devarajan
-
p. 749 - 752
(2013/06/04)
-
- Copper-catalyzed intramolecular N-S bond formation by oxidative dehydrogenative cyclization
-
Copper-catalyzed synthesis of benzo[d]isothiazol-3(2H)-ones and N-acyl-benzothiazetidine by intramolecular dehydrogenative cyclization is described. In this reaction, a new nitrogen-sulfur (N-S) bond is formed by N-H/S-H coupling. The present reaction has
- Wang, Zhen,Kuninobu, Yoichiro,Kanai, Motomu
-
p. 7337 - 7342
(2013/08/15)
-
- A novel kind of dimmer (excimer)-induced-AIE compound 2- phenylisothiazolo[5,4-b]pyridin-3(2H)-one as high selective bisulfite anion probe
-
An interesting dimmer (excimer)-induced-AIE characteristic of 2-phenylisothiazolo[5,4-b]pyridin-3(2H)-one was observed. By using a ring-opening reaction, we developed a novel fluorescent probe based on sub-micron particles of 2-phenylisothiazolo[5,4-b]pyridin-3(2H)-one in water.
- Yang, Bingchuan,Niu, Xiaoyi,Huang, Zixiao,Zhao, Cuihua,Liu, Yang,Ma, Chen
-
supporting information
p. 8250 - 8254
(2013/09/02)
-
- Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors
-
A number of 1,2-benzisothiazol-3-one derivatives were prepared through structural modification of the original compound from high-throughput screening. Some analogues (e.g., 6b, 6r, 6s and 6w) were identified as novel and potent caspase inhibitors with IC50 of nanomolar. Structure-activity relationship (SAR) studies for caspase-3 inhibition were evaluated in vitro. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The present small molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis.
- Liu, Dazhi,Tian, Zhen,Yan, Zhihui,Wu, Lixin,Ma, Yan,Wang, Quan,Liu, Wei,Zhou, Honggang,Yang, Cheng
-
p. 2960 - 2967
(2013/07/28)
-
- An efficient copper mediated synthetic methodology for benzo[d]isothiazol- 3(2H)-ones and related sulfur-nitrogen heterocycles
-
A copper mediated sulfur-nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones and related sulfur-nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur powder, 25-50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.
- Bhakuni, Bhagat Singh,Balkrishna, Shah Jaimin,Kumar, Amit,Kumar, Sangit
-
supporting information; experimental part
p. 1354 - 1357
(2012/04/10)
-
- Synthesis of 1,2-benzisothiazolin-3-ones by ring transformation of 1,3-benzoxathiin-4-one 1-oxides
-
1,2-Benzisothiazolin-3-ones were synthesized from 1,3-benzoxathiin-4-one 1-oxides by means of a nonhazardous and inexpensive method. The 1,3-benzoxathiin-4-one 1-oxides were prepared by oxidation of 1,3-benzoxathiin-4-ones with hydrogen peroxide in the presence of a catalyst. Attack of amines on the carbonyl groups of the 1,3-benzoxathiin-4-one 1-oxides and subsequent elimination of carbonyl compounds likely produced sulfenic acids, which then underwent ring closure to afford the 1,2-benzisothiazolin-3-ones.
- Shimizu, Masao,Shimazaki, Teruaki,Yoshida, Tetsuya,Ando, Wataru,Konakahara, Takeo
-
experimental part
p. 3932 - 3936
(2012/07/14)
-
- Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide-a model for the active-site cysteine of protein tyrosine phosphatase 1B
-
The organometallic anticancer complex [(η6-p-cymene)Ru(en) Cl]PF6 (1, en = ethylenediamine) readily reacts with thiols and forms stable sulfenate/sulfinate adducts which may be important for its biological activity. Protein tyrosine
- Han, Yumiao,Luo, Qun,Hao, Xiang,Li, Xianchan,Wang, Fuyi,Hu, Wenbing,Wu, Kui,Lue, Shuang,Sadler, Peter J.
-
p. 11519 - 11529
(2012/01/04)
-
- Potent, selective, and orally available benzoisothiazolone phosphomannose isomerase inhibitors as probes for congenital disorder of glycosylation Ia
-
We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PMI), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes wit
- Dahl, Russell,Bravo, Yalda,Sharma, Vandana,Ichikawa, Mie,Dhanya, Raveendra-Panickar,Hedrick, Michael,Brown, Brock,Rascon, Justin,Vicchiarelli, Michael,Mangravita-Novo, Arianna,Yang, Li,Stonich, Derek,Su, Ying,Smith, Layton H.,Sergienko, Eduard,Freeze, Hudson H.,Cosford, Nicholas D. P.
-
scheme or table
p. 3661 - 3668
(2011/06/27)
-
- BENZOISOTHIAZOLONES AS INHIBITORS OF PHOSPHOMANNOSE ISOMERASE
-
The disclosure provides new compounds and compositions thereof, and methods for treating or ameliorating a disorder relating to CDG-Ia. In particular, the disclosure provides benzoisothiazolone inhibitors of PMI, which have been synthesized and their abil
- -
-
Page/Page column 35
(2011/10/10)
-
- Crucial role of selenium in the virucidal activity of benzisoselenazol- 3(2h)-ones and related diselenides
-
Various N-substituted benzisoselenazol-3(2H)-ones and their non-seleniumcontaining analogues have been synthesized and tested against selected viruses (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in antiviral activity. The data presented here show that the presence of selenium is crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their isostructural analogues having different groups but lacking selenium either did not show any antiviral activity or their activity was substantially lower. The open-chain analogues of benzisoselenazol- 3(2H)-ones-diselenides also exhibited high antiviral activity while selenides and disulfides were completely inactive towards model viruses.
- Pietka-Ottlik, Magdalena,Potaczek, Piotr,Piasecki, Egbert,Mlochowski, Jacek
-
p. 8214 - 8228
(2011/03/19)
-
- Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer
-
The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C - S)S - S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC50) in BCA2 positive MCF-7 and T47D cells but were inactive (IC50 > 10 μM) in BCA2 negative MDA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve MDA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.
- Brahemi, Ghali,Kona, Fathima R.,Fiasella, Annalisa,Buac, Daniela,Soukupová, Jitka,Brancale, Andrea,Burger, Angelika M.,Westwell, Andrew D.
-
supporting information; experimental part
p. 2757 - 2765
(2010/08/20)
-
- Redox regulation of protein tyrosine phosphatase 1B (PTP1B): A biomimetic study on the unexpected formation of a sulfenyl amide intermediate
-
The effect of steric and electronic environments around the sulfur and nitrogen atoms and the role of nonbonded S...O/N interactions on the cyclization reactions of amide substituted benzene sulfenic acids are described. The reaction profiles and the role
- Sarma, Bani Kanta,Mugesh, Govindasamy
-
p. 8872 - 8881
(2008/02/11)
-
- Phenyliodine(III) bis(trifluoroacetate) mediated synthesis of 2-aryl-1,2-benzisothiazol-3(2H)-ones in ionic liquid
-
Treatment of N-aryl-2-(benzylthio)benzamides with phenyliodine(III) bis(trifluoroacetate) containing trifluoroacetic acid resulted in an interrupted Pummerer-type reaction in ionic liquid 1-n-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6
- Wang, Huey-Min,Liang, I.-Chian,Hou, Rei-Sheu,Huang, Hsin-Yu,Chen, Ling-Ching
-
p. 127 - 130
(2008/02/11)
-
- Novel alternative for the N-S bond formation and its application to the synthesis of benzisothiazol-3-ones
-
(Chemical Equation Presented) The synthesis of a series of benzisothiazolone derivatives starting from the readily available methyl thiosalicylate is presented. The key cyclization step features the formation of a N-acylnitrenium ion, generated by the hypervalent iodine reagent PIFA, and its succeeding intramolecular trapping by the thiole moiety leading to the construction of the title compounds by formation of a new N-S bond.
- Correa, Arkaitz,Tellitu, Imanol,Dominguez, Esther,SanMartin, Raul
-
p. 4811 - 4813
(2007/10/03)
-
- A chemical model for redox regulation of protein tyrosine phosphatase 1B (PTP1B) activity
-
Growing evidence indicates that endogenously produced hydrogen peroxide acts as a cellular signaling molecule that (among other things) can regulate the activity of some protein phosphatases. Recent X-ray crystallographic studies revealed an unexpected chemical transformation underlying the redox regulation of protein tyrosine phosphatase 1B, in which oxidative inactivation of the enzyme yields an intrastrand protein cross-link between the catalytic cysteine residue and its neighboring amide nitrogen. This work describes a small organic molecule that serves as an effective model for the redox-sensing assembly of functional groups at the active site of PTP1B. Findings obtained using this model system suggest that the oxidative transformation of PTP1B to its "crosslinked" inactive form can proceed directly via oxidation of the active-site cysteine to a sulfenic acid (RSOH). The remarkably facile nature of this protein cross-link-forming reaction, along with the widespread cellular occurrence of protein sulfenic acids generated via oxidation of cysteine residues, suggests that the type of oxidative protein cross-link formation first seen in the context of PTP1B represents a potentially general mechanism for redox "switching" of protein function. Thus, the chemistry characterized here could have broad relevance to both redox-regulated signal transduction and the toxic effects of oxidative stress. Copyright
- Sivaramakrishnan, Santhosh,Keerthi, Kripa,Gates, Kent S.
-
p. 10830 - 10831
(2007/10/03)
-
- Synthesis of 1,2-benzisothiazolin-3-one by transamination of sulfenamides
-
N-Substituted sulfenamoylbenzoates were synthesized by transamination of N-unsubstituted sulfenamoylbenzoates with amines. The reaction did not always proceed by simple amine exchange between the amines and ammonia on the sulfur atom of the sulfenamides. In reactions with aliphatic amines, the sulfenamides cyclized to form N-substituted 1,2-benzisothiazolin-3-ones. The synthesis of 1,2-benzisothiazolin-3-ones by intramolecular transamination was also investigated by S-amination of 2-mercaptobenzamides.
- Shimizu, Masao,Takeda, Ayanobu,Fukazawa, Hidenori,Abe, Yoshimoto,Shibuya, Isao
-
p. 1855 - 1864
(2007/10/03)
-
- An effective synthesis of N-substituted 2-sulfenamoylbenzoates and 1,2-benzisothiazolin-3-ones that uses 1,2-benzisothiazolin-3-one as a leaving group
-
N-Substituted 2-sulfenamoylbenzoates and 1,2-benzisothiazolin-3-ones were effectively synthesized by the substitution reaction between S-[2-(3-oxo-1,2-benzisothiazolinyl)]-2-mercaptobenzoates (2) and primary amines. The substitution reaction occurred on the sulfur atom of the 2-sulfenamoyl group of 2, and 1,2-benzisothiazolin-3-one behaved as a leaving group. The eliminated 1,2-benzisothiazolin-3-one could be reused as a starting material for the synthesis of 2. N,N-Disubstituted 2-sulfenamoylbenzoates were prepared by the reaction of 2 with secondary amines.
- Shimizu, Masao,Sugano, Yoshinori,Konakahara, Takeo,Gama, Yasuo,Shibuya, Isao
-
p. 3779 - 3783
(2007/10/03)
-
- An interrupted Pummerer reaction induced by hypervalent iodine(III) reagent: Facile synthesis of 2-aryl-1,2-benzisothiazol-3(2H)-ones
-
Treatment of N-aryl-2-(benzylthio)benzamides with phenyliodine(III) bis(trifluoroacetate) containing trifluoroacetic acid resulted in an interrupted Pummerer-type reaction to give 2-aryl-1,2-benzisothiazol-3(2H)-ones rather than the normal Pummerer-type p
- Wang, Huey-Min,Huang, Hsin-Yu,Kang, Iou-Jiun,Chen, Ling-Ching
-
p. 1231 - 1235
(2007/10/03)
-
- Method for producing alkylsulfinylbenzamides and 1,2-benzisothiazol-3-ones
-
A method for producing an alkylthiobenzamide by carrying out a reaction of a halobenzamide with an alkanethiol in the presence of a base in a heterogeneous solvent; a method for producing an alkylsulfinylbenzamide by carrying out a reaction of an alkylthi
- -
-
-
- Benzyl and t-butyl sulfoxides as sulfenyl halide equivalents: A convenient preparation of benzisothiazolones
-
A new methodology is described for the synthesis of benzisothiazolones from benzylsulfinyl or t-butylsulfinyl substituted carboxamides that provides a mild alternative to conventional cyclization methods that employ halogens.
- Wright,Abelman,Bostrom,Corbett
-
p. 153 - 156
(2007/10/02)
-
- Photochemical Ring-expansion Reaction of 1,2-Benzisothiazolinones
-
The photochemical reaction of a series of 2-aryl-1,2-benzisothiazol-3(2H)-ones (1) under deaerated conditions was found to give dibenzothiazepin-11(10H)-ones (2).A mechanism through a biradical species is proposed for the photoreaction.When the photolysis of 1 was carried out in the presence of oxygen, 2-aryl-1,2-benzisothiazol-3(2H)-one-1-oxides (11) were formed together with compounds 2.
- Kamigata, Nobumasa,Hashimoto, Satoshi,Kobayashi, Michio,Nakanishi, Hiroshi
-
p. 3131 - 3136
(2007/10/02)
-
- A Novel Route to 2-Substituted 1,2-Benzisothiazol-3(2H)-ones
-
2-Alkyl- and 2-aryl-1,2-benzisothiazol-3(2H)-ones were synthesized in high yields by the cyclization of 2-(methylsulphinyl)benzamides with thionyl chloride.
- Uchida, Yuzuru,Kozuka, Seizi
-
p. 510 - 511
(2007/10/02)
-