- A polymerizable Aggregation Induced Emission (AIE)-active dye with remarkable pH fluorescence switching based on benzothiazole and its application in biological imaging
-
In recent years, Aggregation Induced Emission (AIE)-active fluorescent materials have been attracting considerable attention because they play an important role in clinical medicine, photoelectricity, environmental science, biological imaging, and sensors. In this contribution, a novel tetraphenylethylene (TPE) derivative of 2-(4-(1,2,2-triphenylvinyl)benzene) benzothiazole methacrylate (TPBMA) monomer was synthesized by a Suzuki coupling and an acylation reaction using TPE and benzothiazole as structural units, whose maximum emission wavelength respectively appeared at 506 nm in neutral medium and 579 nm in acidic medium with excellent pH sensitivity, and it could change repeatedly at 500 nm and 579 nm under HCl/NH3 fuming, indicating the reversible fluorescence conversion property. As compared with the TPB dye, the emission wavelength of TPBMA spectra has an obvious red-shift, which is consistent with the transition energy level difference (△E) of highest occupied molecular orbital (HOMO) and lowest unoccupied orbital (LUMO) situation by quantum chemistry calculation. Subsequently, the copolymers PEG-TB were successfully prepared by RAFT polymerization of TPBMA and poly (ethylene glycol) monomethacrylate (PEGMA), and their molecular weight (Mw) was about 2.12 × 104 with a narrow polydispersity index (PDI). From the 1H NMR analysis, the actual fraction of TPBMA in the PEG-TB copolymers increased to 22.6% from 17.4% when the feed ratio of TBMTA changed to 25.0% from 20.0%. The obtained PEG-TB could self-assemble into fluorescent organic nanoparticles (FONs) with 100–150 nm diameter in aqueous solution, and their fluorescence intensity increased gradually with the increase of water fraction in the THF solution, indicating the obvious AIE behavior. Moreover, the as-prepared PEG-TB FONs exhibited the prospective potential in the field of biological imaging due to their low cytotoxicity, excellent biocompatibility and easy cells absorption.
- Chen, Weirun,Huang, Zengfang,Li, Jun,Li, Mei,Liu, Xiaobo,Mao, Liucheng,Tao, Lei,Wei, Yen,Yuan, Jinying,Zhou, Chaoyue
-
-
- Facile syntheses of 3-trifluoromethylthio substituted thioflavones and benzothiophenes via the radical cyclization
-
3-CF3S substituted thioflavones and benzothiophenes were achieved via the reactions of AgSCF3 with methylthiolated alkynones and alkynylthioanisoles, respectively, promoted by persulfate. This protocol possesses good functional group tolerance and high yields. Mechanistic studies suggested that a classic two-step radical process was involved, which includes addition of CF3S radical to triple bond and cyclization with SMe moiety.
- Wang, Lu,Wang, Huaiyu,Meng, Weidong,Xu, Xiu-Hua,Huang, Yangen
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supporting information
p. 389 - 392
(2020/03/04)
-
- A Novel Difluoroacetic Acid Derivatives Compound, and Composition Comprising the Same
-
The present invention relates to a novel difluoroacetic acid derivative compound and a composition for various uses containing the same, wherein the difluoroacetic acid derivative compound can not only act as an agonist activating one among PPARandalpha;, andbeta; or andgamma;, but also can exhibit double efficacy or triple efficacy. Therefore, the difluoroacetic acid derivative compound can more effectively prevent, alleviate or treat metabolic diseases in which PPARs involves, and further exhibits whitening and wrinkle alleviation activity, and anti-inflammatory and antioxidant effects, thereby being able to be usefully utilized as various compositions.COPYRIGHT KIPO 2020
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-
-
- Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation
-
While Alzheimer's Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 percentID per g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD. This journal is
- Bandara, Nilantha,Cho, Hong-Jun,Huang, Yiran,Mirica, Liviu M.,Rogers, Buck E.,Sun, Liang,Tran, Diana
-
p. 7789 - 7799
(2020/08/19)
-
- P(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate
-
The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
- Li, Gen,Qin, Ziyang,Radosevich, Alexander T.
-
supporting information
p. 16205 - 16210
(2020/10/26)
-
- Rh-Catalyzed Asymmetric Hydrogenation of Unsaturated Medium-Ring NH Lactams: Highly Enantioselective Synthesis of N-Unprotected 2,3-Dihydro-1,5-benzothiazepinones
-
A straightforward method to prepare 1,5-benzothiazepines was reported. Catalyzed by a Rh/Zhaophos complex, unsaturated cyclic NH lactams with a medium-size ring were hydrogenated smoothly, giving remarkably high enantioselectivities. The sulfur atom in the substrates did not bring an inhibition which was observed with commercially available bisphosphine ligands. This method was successfully applied in the scale-up synthesis of (R)-(-)-thiazesim.
- Yin, Congcong,Yang, Tao,Pan, Yingmin,Wen, Jialin,Zhang, Xumu
-
supporting information
p. 920 - 923
(2020/02/04)
-
- PROTEOLYSIS TARGETING CHIMERIC (PROTAC) COMPOUND WITH E3 UBIQUITIN LIGASE BINDING ACTIVITY AND TARGETING ALPHA-SYNUCLEIN PROTEIN FOR TREATING NEURODEGENERATIVE DISEASES
-
The present disclosure relates to bifunctional compounds, which find utility as modulators of alpha-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/ inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. Such diseases or disorders are alpha-synucleinopathies or neurodegenerative diseases associated with alpha-synuclein accumulation and aggregation, such as e.g. Parkinson Disease, Alzheimer's Disease, dementia, dementia with Lewy bodies or multiple system atrophy, in particular Parkinson's Disease.
- -
-
Paragraph 00416-00417
(2020/03/15)
-
- Synthesis and crystal structure of 7-bromo-3,3-dibutyl-8-methoxy-5-phenyl-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one
-
7-Bromo-3,3-dibutyl-8-methoxy-5-phenyl-2,3-dihydrobenzo[b][1,4]thiazepin-4(5H)-one is prepared from 6-methoxybenzo[d]thiazol-2-amine and 2-(bromomethyl)-2-butylhexanoic acid as the key starting materials via five simple steps including hydrolysis, substit
- Du, Damin,Wu, Haijian
-
p. 437 - 440
(2020/03/23)
-
- Convenient and efficient synthesis of novel 11: H -benzo[5,6][1,4]thiazino[3,4- a] isoindol-11-ones derived from 2-bromo-(2/3-substitutedphenyl)-1 H -indene-1,3(2 H)-diones
-
An unprecedented formation of 11H-benzo[5,6][1,4]thiazino[3,4-a]isoindol-11-ones through a one-step reaction of differently substituted 2-aminobenzenethiols and 2-bromo-(2/3-substitutedphenyl)-1H-indene-1,3(2H)-diones in freshly dried ethanol under reflux conditions has been investigated. This unique transformation probably occurs through an initial nucleophilic substitution followed by ring opening and subsequent intramolecular cyclization. The structures of all the synthesized benzo[1,4]thiazino isoindolinones were established by FTIR, 1H NMR, 13C NMR, HRMS, and X-ray crystallographic analysis. This approach was found to be simple and convenient and provides several advantages such as substantial atom economy, short reaction time and operational simplicity.
- Mor, Satbir,Sindhu, Suchita
-
p. 12784 - 12792
(2019/05/10)
-
- Compounds with high selectivity to tau aggregates, tau-targeting probe comprising the same, and preparation method thereof
-
The present invention relates to: a compound represented by chemical formula 1, which exhibits excellent binding force to tau aggregates, thereby being useful for early diagnosis of degenerative brain diseases including dementia, and for preventing and treating the same; a method for manufacturing the same; and a pharmaceutical composition comprising the same. The compound according to the present invention exhibits a high selectivity to tau aggregates compared to beta amyloid, and thus the compound can be usefully used for the early diagnosis and prevention or treatment of diseases related to tau aggregates including dementia.COPYRIGHT KIPO 2019
- -
-
Paragraph 0169-0172
(2019/09/14)
-
- Compounds with high selectivity to tau aggregates, tau-targeting probe comprising the same, and preparation method thereof
-
The present invention relates to: a compound represented by chemical formula 1, which exhibits excellent binding force to tau aggregates, thereby being useful for early diagnosis of degenerative brain diseases including dementia, and for preventing and treating the same; a method for manufacturing the same; and a pharmaceutical composition comprising the same. The compound according to the present invention exhibits a high selectivity to tau aggregates compared to beta amyloid, thereby being able to be usefully used for early diagnosis, prevention or treatment of diseases related to tau aggregates including dementia.COPYRIGHT KIPO 2020
- -
-
Paragraph 0169-0172
(2020/04/01)
-
- THERAPEUTIC COMPOUNDS
-
The invention provides compounds having the general formula I: and pharmaceutically acceptable salts thereof, wherein the variables R1, R2, R3, R4, subscipt m and n, have the meaning as described herein, and com
- -
-
Page/Page column 12; 17
(2018/03/25)
-
- Synthesis of Indane-Based 1,5-Benzothiazepines Derived from 3-Phenyl-2,3-dihydro-1H-inden-1-one and Antimicrobial Studies Thereof
-
In the present study, a series of 20 indane-based 1,5-benzothiazepines (5a–t) has been prepared derived from 3-phenyl-2,3-dihydro-1H-inden-1-one (1). All the synthesized 1,5-benzothiazepines (5a–t) were screened for their in vitro antimicrobial activities against four bacteria [Bacillus subtilis (MTCC 441), Staphylococcus epidermidis (MTCC 6880), Escherichia coli (MTCC 1652), and Pseudomonas aeruginosa (MTCC 424)] and two fungi [Candida albicans (MTCC 227) and Aspergillus niger (MTCC 8189)]. Among all the tested derivatives, 5n and 5o against E.?coli displayed more inhibitory activity than that of the reference drug, ciprofloxacin, while the derivatives 5c, 5m–o, 5s, and 5t against C.?albicans, and 5d, 5e, 5n, 5o, 5s, and 5t against A.?niger were found to be more potent than the standard drug, that is, fluconazole.
- Mor, Satbir,Nagoria, Savita,Sindhu, Suchita,Khatri, Mohini,Sidhu, Gurdeep,Singh, Virender
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p. 3282 - 3293
(2017/10/06)
-
- NOVEL AMINOALKYL BENZOTHIAZEPINE DERIVATIVE AND USE THEREOF
-
The present invention relates to a novel aminoalkylbenzothiazepine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for preventing or treating constipation comprising the same as an active ingredient.
- -
-
Paragraph 004; 0045
(2017/09/05)
-
- Lipophilic methylene violet analogues as modulators of mitochondrial function and dysfunction
-
In an effort to identify methylene blue analogues having improved antioxidant activity, a series of new methylene violet analogues have been designed and synthesized. The analogues were prepared following a synthetic route that is more efficient than the
- Roy Chowdhury, Sandipan,Khdour, Omar M.,Bandyopadhyay, Indrajit,Hecht, Sidney M.
-
p. 5537 - 5547
(2017/10/09)
-
- Efficient and convenient synthesis, characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines
-
In the present study, 20 new tetracyclic 1,4-benzothiazines (4a-4 t) were conveniently synthesized in good yields and characterized by different spectral and physical techniques. The in vitro antimicrobial evaluation of the synthesized benzothiazine derivatives was performed by serial dilution against two Gram-positive bacteria [Bacillus subtilis (MTCC 441) and Staphylococcus epidermidis (MTCC 6880)], two Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)], and two fungal strains [Candida albicans (MTCC 227) and Aspergillus Niger (MTCC 8189)]. The derivatives 4 l and 4 t were found to be more potent than standard drug, i.e., fluconazole, against A. Niger and C. albicans, respectively.
- Mor, Satbir,Nagoria, Savita
-
p. 169 - 178
(2016/02/23)
-
- Containing three styrene or four styrene structure with aggregation inducing light-emitting performance of the benzothiazole derivative and its preparation method and application
-
The invention discloses a benzothiazole derivative containing a triphenylethylene or tetraphenylethylene structure and having aggregation-induced emission property and a preparation method and application thereof. The preparation method comprises the foll
- -
-
Paragraph 0047-0049
(2016/12/01)
-
- PHENOTHIAZINE ANALOGUES AS MITOCHONDRIAL THERAPEUTIC AGENTS
-
The present disclosure provides phenothiazine derivative compounds and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications, such as treatment or suppression of diseases associated with
- -
-
Paragraph 0125; 0158
(2016/09/15)
-
- Synthesis of bioactive substituted pyrazolylbenzothiazinones
-
Abstract Pyrazolylbenzothiazinones have been synthesized in good yields by the reaction of 2-hydrazinocarbonymethyl-3,4-dihydro-2H-1,4-benzothiazin-3-ones with β-diketone in the presence of ethanol. The structures of synthesized pyrazolylbenzothiazinones were confirmed on the basis of their analytical and spectral data. The antimicrobial activities of the synthesized compounds have also been included.
- Sharma, Praveen Kumar,Kumar
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p. 6141 - 6148
(2015/08/18)
-
- The flocculated acryloyldimethyltauric molecule ligand
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Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example: formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.
- -
-
Paragraph 0434; 0435
(2016/10/08)
-
- Synthesis and structure-activity relationships of gadolinium complexes of DO3A-benzothiazole conjugates as potential theranostic agents
-
The synthesis of two bifunctional chelates, 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) conjugates of benzothiazoles (H3L3a and H3L3b), and the corresponding gadolinium complexes (GdL3a
- Jung, Ki-Hye,Kang, Sun-Hee,Kang, Min-Kyoung,Kim, Soyeon,Kim, Hee-Kyung,Kim, Yeoun-Hee,Ho Lee, Gang,Shim, Gyu-Bo,Jung, Jae-Chang,Chang, Yongmin,Kim, Tae-Jeong
-
supporting information
p. 599 - 604
(2015/02/19)
-
- Functionalized tricyclic cytosine analogues provide nucleoside fluorophores with improved photophysical properties and a range of solvent sensitivities
-
Tricyclic cytosines (tC and tCO frameworks) have emerged as a unique class of fluorescent nucleobase analogues that minimally perturb the structure of B-form DNA and that are not quenched in duplex nucleic acids. Systematic derivatization of th
- Rodgers, Brittney J.,Elsharif, Nada A.,Vashisht, Nisha,Mingus, MacY M.,Mulvahill, Mark A.,Stengel, Gudrun,Kuchta, Robert D.,Purse, Byron W.
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supporting information
p. 2010 - 2015
(2014/03/21)
-
- FLUORESCENT PROBES FOR DETECTION OF COPPER
-
The invention provides fluorescent sensors for the selective detection of a metal such as copper. The sensors may be considered to be derivatives of cyanine, fluorescein, rhodamine, rhodol, Tokyo green, or BODIPY. The sensors find particular use in detecting copper in cells and living animals.
- -
-
Paragraph 0213-0215
(2014/03/24)
-
- Synthesis and evaluation of the anticonvulsant activity of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4]thiazepine derivatives
-
Two series of 8-alkoxy-4,5-dihydrobenzo[b][1,2,4]triazolo[4,3-d][1,4] thiazepine derivatives (6a-q and 7a-q) were synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. All of the compounds prepared were e
- Deng, Xian-Qing,Song, Ming-Xia,Wang, Shi-Ben,Quan, Zhe-Shan
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p. 272 - 280
(2014/04/03)
-
- Synthesis and anticonvulsant activity evaluation of 7-alkoxy-2, 4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-ones in various murine experimental seizure models
-
A novel series of 7-alkoxy-2,4-dihydro-1H-benzo [b][1,2,4]triazolo[4,3-d] [1,4]-thiazin-1-ones have been synthesized and tested for their anticonvulsant activity using the maximal electroshock (MES) method. The majority of the compounds prepared were effe
- Cao, Xu,Wang, Shi-Ben,Deng, Xian-Qing,Liu, Da-Chuan,Quan, Zhe-Shan
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p. 1829 - 1838
(2014/05/06)
-
- An AIE-active luminophore with tunable and remarkable fluorescence switching based on the piezo and protonation-deprotonation control
-
A novel luminophore TPENSOH was facilely synthesized from the building blocks of tetraphenylethylene and 6-hydroxylbenzothiazole and exhibited unique AIE properties. This new dye was found to show a remarkable and reversible four-color switching based on
- Ma, Chunping,Xu, Bingjia,Xie, Gaoyi,He, Jiajun,Zhou, Xie,Peng, Bangyin,Jiang, Long,Xu, Bin,Tian, Wenjing,Chi, Zhenguo,Liu, Siwei,Zhang, Yi,Xu, Jiarui
-
supporting information
p. 7374 - 7377
(2014/07/07)
-
- TRI-HETEROCYCLIC DERIVATIVES, PREPARATION PROCESS AND USES THEREOF
-
The present invention relates to a tri-heterocyclic derivatives, preparation process and uses thereof, specifically relates to a tri-heterocyclic derivatives of the formula (I) or a pharmaceutically acceptable salt thereof, preparation process, and further relates to a pharmaceutically acceptable composition comprising compounds of formula (I), or a pharmaceutically acceptable salt thereof, and their pharmaceutical use as inhibitors of kinase.
- -
-
Paragraph 0121; 0222
(2014/11/13)
-
- TRI-HETEROCYCLIC DERIVATIVES, PREPARATION PROCESS AND USES THEREOF
-
The present invention relates to a tri-heterocyclic derivatives, preparation process and uses thereof, specifically relates to a tri-heterocyclic derivatives of the formula (I) or a pharmaceutically acceptable salt thereof, preparation process, and further relates to a pharmaceutically acceptable composition comprising compounds of formula (I), or a pharmaceutically acceptable salt thereof, and their pharmaceutical use as inhibitors of kinase
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-
Page/Page column 28-29
(2013/07/05)
-
- Synthesis and evaluation of novel 18f labeled 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives as ligands for positron emission tomography (PET) imaging of β-amyloid plaques
-
A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ1-42 aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for 18F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [18F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N- methylpyridin-2-amine ([18F]32) (Ki = 8.0 ± 3.2 nM) displayed a brain2min/brain60min ratio of 4.66, which is highly desirable for Aβ imaging agents. Target specific binding of [ 18F]32 to Aβ plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [18F]32 is a promising Aβ imaging agent for PET and merits further evaluation in human subjects.
- Cui, Mengchao,Wang, Xuedan,Yu, Pingrong,Zhang, Jinming,Li, Zijing,Zhang, Xiaojun,Yang, Yanping,Ono, Masahiro,Jia, Hongmei,Saji, Hideo,Liu, Boli
-
p. 9283 - 9296
(2013/01/15)
-
- Synthesis and antimicrobial activity of structurally flexible heterocycles with the 1,4-thiazine heterosystem
-
In this work, 4H-1,4-benzothiazines were synthesized by an efficient synthetic method in a single step involving heterocyclization of substituted 2-aminobenzenethiols with β-ketoester. The structures of the synthesized compounds were confirmed by their analytical and spectral data. The synthesized compounds were evaluated for their antimicrobial activity against bacterial species; E. coli and Bacillus cereus. The synthesized compounds showed significant activity against microorganisms, which can be correlated with the privileged heterocyclic structural scaffolds.
- Sharma, Praveen Kumar,Fogla, Ankur,Rathore,Kumar
-
experimental part
p. 1103 - 1111
(2012/04/17)
-
- Pyrrolopyrrole cyanines: Effect of substituents on optical properties
-
To tune their optical properties, a large variety of pyrrolopyrrole cyanines (PPCys) were synthesized with substitutedheteroaromatics such as quinoline, benzothiazole, and oxazole derivatives as terminal groups. Thus, a broad range of stable, highly fluorescing near-infrared (NIR) dyes with high absorptivities between 690 to 845 nm is accessible. The large number of newly synthesized compounds allows a detailed discussion of the correlation between molecular structure and the optical properties of the first electronic transition. Syntheses and optical properties of pyrrolopyrrole cyanines (PPCys) with different substituents at the terminal heteroaromatic moieties are described. The relationship between molecular structure and optical properties is discussed. By suitable substitution, the absorption and fluorescence maxima of the chromophore can be tuned in a range between 690 and 845 nm. Copyright
- Fischer, Georg M.,Klein, Matthias K.,Daltrozzo, Ewald,Zumbusch, Andreas
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p. 3421 - 3429
(2011/09/12)
-
- Fluorescence properties of 5-(5,6-dimethoxybenzothiazol-2-yl)-2′- deoxyuridine (dbtU) and oligodeoxyribonucleotides containing d btU
-
We describe the synthesis and photophysical properties of 11 substituted 5-(benzothiazol-2-yl)-2′-deoxyuridine derivatives and oligodeoxyribonucleotides (ODNs) containing 5-(5,6-dimethoxybenzothiazol-2-yl)- 2′-deoxyuridine (dbtU), which was the strongest fluorescent derivative among those prepared. The fluorescence properties of dbtU itself and ODNs containing dbtU show the same tendency of being weaker in both neutral and acidic solution and stronger in basic solution. The ODNs (15mer) containing 16 combinations of 5′-XbtU-3′ and 5′-btUY-3′, where X, Y = A, T, G, or C, were synthesized, and their fluorescence intensity and quantum yield in basic solution were compared. On average, only the ODN with the 5′-G btU-3′ sequence shows a 7.9-fold lower fluorescence intensity than the other sequences. Ab initio calculations of 5′-G btU-3′ and 5′-btUG-3′ as models under basic conditions suggest that the lower fluorescence of the ODN containing the 5′-GbtU-3′ sequence is caused by a wider overlap between stacked guanine (Gua) and btUra than that of the 5′- btUG-3′ sequence and that the HOMO is delocalized not only on btUra but also on Gua.
- Hirose, Wataru,Sato, Kousuke,Matsuda, Akira
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p. 6206 - 6217
(2011/12/02)
-
- Facile synthesis of bioactive 4H-[1,4]-benzothiazines under solvent free conditions
-
An efficient method for synthesis of 4H-[1,4]-benzothiazines under solvent free conditions has been developed. The oxidative condensation of 2-aminobenzenethiols with β-diketones/β-ketoesters in presence of catalytic amount of hydrazine hydrate yields the 4H-[1,4]-benzothiazines. The reaction is accelerated by microwave irradiation under solvent free conditions in presence of an energy transfer agent DMF to get the product in high yield. The 2-aminobenzenethiazole required for the synthesis of 4H-[1,4]-benzothiazines are also obtained by a new method instead of presently used time consuming and low yielding method. The structure of the synthesized compounds has been characterized by IR, NMR, mass spectral studies and elemental analysis.
- Kalwania,Chomal,Choudhary, Savita
-
p. 5133 - 5136
(2012/06/18)
-
- NEW IMAGING AGENTS AND THEIR USE FOR THE DIAGNOSTIC IN VIVO OF NEURODEGENERATIVE DISEASES, NOTABLY ALZHEIMER'S DISEASE AND DERIVATIVE DISEASES
-
The present invention relates to new imaging agents and their use for the in vivo diagnostic of neurodegenerative diseases, notably Alzheimer's disease and related diseases.
- -
-
Page/Page column 38; 39
(2011/05/05)
-
- Synthesis and anticonvulsant activity of some 7-alkoxy-2H-1,4-benzothiazin- 3(4H)-ones and 7-alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazines
-
A series of 7-alkoxy-2H-1,4-benzothiazin-3(4H)-ones and a new series of 7-alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazine derivatives were synthesized using 5-methoxybenzo[d]thiazol-2-amine as starting material. The structures of the compounds were
- Zhang, Li-Qiu,Guan, Li-Ping,Wei, Cheng-Xi,Deng, Xian-Qing,Quan, Zhe-Shan
-
experimental part
p. 326 - 331
(2011/02/25)
-
- Creating an antibacterial with in vivo efficacy: Synthesis and characterization of potent inhibitors of the bacterial cell division protein FTSZ with improved pharmaceutical properties
-
3-Methoxybenzamide (1) is a weak inhibitor of the essential bacterial cell division protein FtsZ. Alkyl derivatives of 1 are potent antistaphylococcal compounds with suboptimal drug-like properties. Exploration of the structure-activity relationships of analogues of these inhibitors led to the identification of potent antistaphylococcal compounds with improved pharmaceutical properties.
- Haydon, David J.,Bennett, James M.,Brown, David,Collins, Ian,Galbraith, Greta,Lancett, Paul,MacDonald, Rebecca,Stokes, Neil R.,Chauhan, Pramod K.,Sutariya, Jignesh K.,Nayal, Narendra,Srivastava, Anil,Beanland, Joy,Hall, Robin,Henstock, Vincent,Noula, Caterina,Rockley, Chris,Czaplewski, Lloyd
-
supporting information; experimental part
p. 3927 - 3936
(2010/09/04)
-
- Synthesis and evaluation of novel benzothiazole derivatives based on the bithiophene structure as potential radiotracers for β-amyloid plaques in Alzheimer's disease
-
In this study, six novel benzothiazole derivatives based on the bithiophene structure were developed as potential β-amyloid probes. In vitro binding studies using Aβ aggregates showed that all of them demonstrated high binding affinities with Ki/sub
- Cui, Meng-Chao,Li, Zi-Jing,Tang, Rui-Kun,Liu, Bo-Li
-
experimental part
p. 2777 - 2784
(2010/07/04)
-
- Synthesis and cyclization of N-{2-[(2-carboxyethyl)sulfanylphenyl]}-β- alanines*
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The reaction of methyl- and methoxyaminobenzenethiols with acrylic acid resulted in formation of 8-methyl- and 8-methoxy-2,3-dihydro-1,5-benzothiazepin- 4(5H)-ones, N-{2-[(2-carboxyethyl)sulfanyl]-4-methylphenyl}-β-alanine and 3-[(8-methoxy-4-oxo-3,4-dihydro-1,5-benzothiazepin-5(2H)-yl]propanoic acid. Their cyclization to N- (5-methyl-4-oxo-3,4-dihydro-2H-thiochromen-8-yl)-β- alanine, 5-methy l-9,10-dihydro-2H-thiopyrano[3,2-h]quinoline-4,7(3H, 8H)-dione and 10-methyl-2,3,6,7-tetrahydro-4H, 8H-[1,4]thiazepino[2,3,4-ij]quinoline-4,8- dione is described.
- Rutkauskas,Kantminiene,Beresnevicius
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experimental part
p. 2341 - 2347
(2009/04/10)
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- DIAGNOSTIC AND REMEDY FOR DISEASE CAUSED BY AMYLOID AGGREGATION AND/OR DEPOSITION
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To provide a diagnostic drug which binds specifically to an amyloid aggregate and/or an amyloid deposit, to thereby realize imaging and quantification of a disease caused by amyloid aggregation and/or deposition. The invention provides a compound represented by formula (1) : (wherein X1 represents an optionally substituted bicyclic heterocyclic group; X2 represents a hydrogen atom, a halogen atom, or a chelate-forming group; ring A represents a benzene ring or a pyridine ring; and ring B represents an optionally substituted 5-membered aromatic heterocyclic group which is bonded to the benzene ring or the pyridine ring via a carbon atom of ring B), a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these, and a diagnostic, preventive, or therapeutic drug containing the same.
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Page/Page column 28-29
(2008/12/07)
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- FLUORINATION PROCESS OF ANILIDE DERIVATIVES AND BENZOTHIAZOLE FLUORINATE DERIVATIVES AS IN VIVO IMAGING AGENTS
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The invention relates to a process for preparation of a compound of formula (I): R1 is selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl ; which comprises: (i) reaction with fluoride, suitably [18F]fluoride, of a corresponding compound of formula (II): wherein R2 is selected from hydrogen, C1-10alkyl, C1-10haloalkyl, C6-14aryl,C6-14arylalkyl, -(CH2CH2O)q-CH3wherein q is an integer of from 1 to 10; R1 is as defined for the compound of formula (I); and R3 is a leaving group. Certain novel precursors of formula (II) and radiopharmaceutical kits containing such precursors are also claimed.
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Page/Page column 21-22
(2010/11/26)
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- Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17β-hydroxysteroid dehydrogenase type 3
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A novel series of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) inhibitors has been identified. These inhibitors, based on a dibenzazocine core, exhibited picomolar to low nanomolar inhibition of 17β-HSD3 in cell-free enzymatic as well as in cell-based transcriptional reporter assays.
- Fink, Brian E.,Gavai, Ashvinikumar V.,Tokarski, John S.,Goyal, Bindu,Misra, Raj,Xiao, Hai-Yun,Kimball, S. David,Han, Wen-Ching,Norris, Derek,Spires, Thomas E.,You, Dan,Gottardis, Marco M.,Lorenzi, Matthew V.,Vite, Gregory D.
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p. 1532 - 1536
(2007/10/03)
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- Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents.
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The synthesis and evaluation of a series of neutral analogues of thioflavin-T (termed BTA's) with high affinities for aggregated amyloid and a wide range of lipophilicities are reported. Radiolabeling with high specific activity [(11)C]methyl iodide provided derivatives for in vivo evaluation. Brain entry in control mice and baboons was high for nearly all of the analogues at early times after injection, but the clearance rate of radioactivity from brain tissue varied by more than 1 order of magnitude. Upon the basis of its rapid clearance from normal mouse and baboon brain tissues, [N-methyl-(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]6-OH-BTA-1) was selected as the lead compound for further evaluation. The radiolabeled metabolites of [(11)C]6-OH-BTA-1 were polar and did not enter brain. The binding affinities of [N-methyl-(3)H]6-OH-BTA-1 for homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils were similar (K(d) = 1.4 nM and 4.7 nM, respectively), but the ligand-to-Abeta peptide binding stoichiometry was approximately 400-fold higher for AD brain than Abeta(1-40) fibrils. Staining of AD frontal cortex tissue sections with 6-OH-BTA-1 indicated the selective binding of the compound to amyloid plaques and cerebrovascular amyloid. The encouraging in vitro and in vivo properties of [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition.
- Mathis, Chester A,Wang, Yanming,Holt, Daniel P,Huang, Guo-Feng,Debnath, Manik L,Klunk, William E
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p. 2740 - 2754
(2007/10/03)
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- Pharmacological profile of 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b] [1,4]benzothiazin-6-one, a novel human estrogen receptor agonist
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Pharmacological studies were carried out to characterize further the endocrinological profile and the binding mode to the estrogen receptor (ER) of 6,12-dihydro-3-methoxy-l-benzopyrano[3,4-b][1,4]benzothiazin-6-one (1). Binding experiments were conducted with highly purified recombinant human estrogen receptors hERα and β. Potent estrogenic activity of compound 1 was assessed by testing its ability to down-regulate ERs and to enhance estrogen receptor element (ERE)-dependent transcription. The latest step of our work dealt with the synthesis of the 9-fluorinated derivative 15 for ionic microscopy experiments to determine the intracellular localization of compound 1. Although 1 failed to compete with [3H]E2 for binding to both ER isoforms, evidence was reported that it interacted with hERα in MCF-7 cells (ER down-regulation/ERE-dependent luciferase induction). Hence, an appropriate conformation of the hormone binding domain, most probably conferred by co-regulators of ER, is required for the onset of an activity of the compound 1. Estrogenic activity was weak but on the order of magnitude of that of coumestrol (slightly weaker). The synthesis of the 9-methoxylated derivative 16 and its pharmacological evaluation led us to propose a binding mode of 1 on hERα. Compound 1 appears to interact with ERα mainly through interactions of its 3-methoxy substituent with the residue His-524 of the hormone binding domain.
- Jacquot, Yves,Cleeren, Anny,Laios, Ioanna,Ma, Yan,Boulahdour, Athem,Bermont, Laurent,Refouvelet, Bernard,Adessi, Gerard,Leclercq, Guy,Xicluna, Alain
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p. 335 - 341
(2007/10/03)
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- Hypolipidemic benzothiazepines
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The invention is concerned with novel hypolipidemic compounds of formula (I), with processes and novel intermediates for their preparation, pharmaceutical compositions containing them and with their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions, and associated diseases such as atherosclerosis. STR1
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- Benzothiazoles and benzoxazoles, drugs containing them, their use and methods of preparing them
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The invention relates to benzothiazoles and benzoxazoles of general formula STR1 wherein R1 to R3, X, Z and n are defined as in claim 1, the enantiomers, diastereomers and salts thereof, particularly the physiologically acceptable acid addition salts thereof which have valuable properties, particularly an inhibitory effect on cholesterol biosynthesis, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them.
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- Antiviral dibenzothiazepinone derivatives
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Compounds of formula (I) wherein n is 0, 1 or 2; and R1 and R2, which may be the same or different, each represent one or more ring substituent(s) selected from: hydrogen, hydroxy, halogen, cyano, nitro, C1-6 alkyl, C3-6 cycloalkyl or C1-6 alkoxy (where the alkyl or cycloalkyl moiety may be optionally substituted by one or more substituents selected from halogen atoms and hydroxyl groups); --NR4 R5 where R4 and R5, which may be the same or different, each represent hydrogen or C1-6 alkyl; --S(O)m R6, where m is 0, 1, 2 or 3 and R6 represents hydrogen, C1-6 alkyl or C3-6 cycloakyl; --SO2 NR4 R5 where R4 et R5 are each as defined above; phenyl, phenylC1-3 alkoxy or phenylC1-3 alkyl where the phenyl group may be optionally substituted by one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, hydroxy, nitro, halogen and amino; and --CO2 H or --COR7 where R7 is C1-6 alkyl or C3-6 cycloalkyl; R3 represents hydrogen or C1-4 alkyl; and esters, salts and other physiologically functional derivatives thereof; show activity as antiviral agents, for example against HIV. Certain of the compounds are novel.
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- Synthesis and biological evaluation of alkyl, alkoxy, alkylthio, or amino-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones
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2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones substituted with an alkyl, alkoxy, alkylthio, hydroxy, or amino group on the fused benzene ring of the 1,5-benzothiazepine skeleton were synthesized and their vasodilating, antihypertensive, and platelet aggregation-inhibitory activities were investigated. (-)-cis-3-Acetoxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-8- methyl-2-(4-methylphenyl)-1,5-benzothiazepin-4(5H)-one ((-)-13e) was selected for further studies as a potent inhibitor of platelet aggregation.
- Inoue, Hirozumi,Konda, Mikihiko,Hashiyama, Tomiki,Otsuka, Hisao,Watanabe, Akishige,Gaino, Mitsunori,Takahashi, Kaoru,Date, Tadamasa,Okamura, Kimio,Takeda, Mikio,Narita, Hiroshi,Murata, Sakae,Odawara, Akio,Sasaki, Haruhiko,Nagao, Taku
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p. 1008 - 1026
(2007/10/03)
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- Synthesis of some new 1,4-benzothiazines and their anti psychotic activity
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1,4-Benzothiazines (1-28) have been synthesized by treating substituted aminothiophenols with various substituted β-diketones in the presence of piperidine in THF solution.
- Chaudhari,Shinde,Shingare
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p. 1250 - 1256
(2007/10/03)
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- Dibenzothiazepinthione as antiviral agents
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Compounds of formula (I) wherein n is 0, 1 or 2; and R1 and R2, which may be the same or different, each represent one or more ring substituent(s) selected from: hydroxy, halogen, cyano, nitro, C1-6 alkyl, C3-6 cycloalkyl or C1-6 alkoxy (where the alkyl or cycloalkyl moiety may be optionally substituted by one or more substituents selected from halogen atoms and hydroxyl groups); --NR4 R5 where R4 and R5 which may be the same or different, each represent hydrogen or C1-6 are each as defined above; phenyl, phenyl C1-3 alkoxy or phenyl C1-3 alkyl where the phenyl group may be optionally substituted by one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, hydroxy, nitro, halogen and amino; and --CO2 H or --COR7 where R7 is C1-6 alkyl or C3-6 cycloalkyl; R3 is hydrogen or C1-4 alkyl: and esters, salts and other physiologically functional derivatives thereof, show activity as antiviral agents, for example against HIV. The majority of the compounds are novel.
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- PYRIMIDO-BENZOTHIAZINES
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This invention relates to novel pyrimido-benzothiazine derivative compounds. The compounds of the present invention inhibit the action of the lipoxygenase enzyme and are useful in the treatment or alleviation of inflammatory diseases, allergy and cardiovascular diseases in mammals. this invention also relates to pharmaceutical compositions comprising such compounds.
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