- Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist
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Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound27h(designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC50) value of 64 nM and showed excellent selectivity against other nuclear receptors.27halso potently suppressed cell proliferation, colony formation, and the expression of androgen receptor (AR)-regulated genes in AR-positive prostate cancer cell lines. In addition,27hdemonstrated good metabolic stability and a pharmacokinetic property with reasonable oral bioavailability (32.41%) and moderate half-life (t1/2= 4.98 h). Significantly, oral administration of compound27hachieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound27hmay serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
- Wu, Xishan,Shen, Hui,Zhang, Yan,Wang, Chao,Li, Qiu,Zhang, Cheng,Zhuang, Xiaoxi,Li, Chenchang,Shi, Yudan,Xing, Yanli,Xiang, Qiuping,Xu, Jinxin,Wu, Donghai,Liu, Jinsong,Xu, Yong
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supporting information
p. 8775 - 8797
(2021/06/30)
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- Facile syntheses of 3-trifluoromethylthio substituted thioflavones and benzothiophenes via the radical cyclization
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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)
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- A Novel Difluoroacetic Acid Derivatives Compound, and Composition Comprising the Same
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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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- 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
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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
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p. 12784 - 12792
(2019/05/10)
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- Novel SIRT 1 activator and medical use thereof
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The present invention relates to a SIRT 1 activator and medical uses thereof. In the present invention, a novel SIRT 1 activator compound based on a benzo[d]thiazole skeleton, a crystalline form thereof, a hydrate thereof or a salt thereof is prepared, and effect on alleviating obesity, insulin resistance and dyslipidemia, alleviating fatty liver, preventing cell aging, preventing oxidative stress and extending of life of yeast. Therefore, the novel SIRT 1 activator compound having the above effects can be used for a pharmaceutical composition for therapeutic use for preventing or treating metabolic diseases including obesity, diabetes mellitus, dyslipidemia and the like and liver diseases including alcoholic or non-alcoholic fatty liver, fatty liver diseases and the like, and a health food composition for alleviating cell aging or prolonging the life span, and the like.COPYRIGHT KIPO 2018
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- Synthesis of Indane-Based 1,5-Benzothiazepines Derived from 3-Phenyl-2,3-dihydro-1H-inden-1-one and Antimicrobial Studies Thereof
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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)
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- Natural Product-Mimetic Scaffolds with Privileged Heterocyclic Systems: Design, Synthesis, and Evaluation of Antioxidant Activity of Quinazoquinobenzothiazinones
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(Chemical Equation Presented) Structurally diverse quinazolinoquinolinobenzothiazinones based on rutaecarpine structural framework with hybrid structural features of three medicinally privileged heterocyclic systems has been synthesized as natural product-mimetic scaffolds involving the use of multi-step reaction sequences. The synthesized quinazolinoquinolinobenzothiazinones have been evaluated for their antioxidant and radical scavenging activities.
- Sharma, Kshitija,Khandelwal, Sarita,Samarth,Kumar, Mahendra
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p. 220 - 228
(2016/02/10)
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- Efficient and convenient synthesis, characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines
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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
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supporting information
p. 169 - 178
(2016/02/23)
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- COMPOUNDS FOR THE MODULATION OF MYC ACTIVITY
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The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject.
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Paragraph 530; 531-532
(2017/01/31)
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- 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.
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Paragraph 0785; 0786
(2016/10/08)
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- Synthesis of bioactive substituted pyrazolylbenzothiazinones
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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)
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- Synthesis and antimicrobial activity of structurally flexible heterocycles with the 1,4-thiazine heterosystem
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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
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experimental part
p. 1103 - 1111
(2012/04/17)
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- Facile synthesis of bioactive 4H-[1,4]-benzothiazines under solvent free conditions
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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
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p. 5133 - 5136
(2012/06/18)
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- Evaluation of Re and 99mTc complexes of 2-(4′-aminophenyl) benzothiazole as potential breast cancer radiopharmaceuticals
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The synthesis of M(I)(CO)3(NNO) (M = Re, 99mTc) complexes conjugated to the antitumor agent 2-(4′-aminophenyl) benzothiazole and to its 6-methyl derivative, as well as their in vitro and in vivo biological evaluation as breast cancer radiopharmaceuticals, is reported. The Re complexes displayed under the fluorescence microscope clear uptake by the sensitive to the 2-(4′-aminophenyl)benzothiazole pharmacophore breast cancer cell lines MCF-7 and T47D, while uptake by less sensitive lines and by normal fibroblasts was much weaker. In accordance, uptake of the corresponding radioactive 99mTc complexes was clearly higher in the breast cancer cell lines MCF-7 and MDA-231 compared to normal fibroblasts. Biodistribution of the 99mTc complexes in SCID mice bearing MCF-7 xenografts showed appreciable tumor uptake. A tumor/muscle ratio of 2.2 was measured for the complex conjugated to 2-(4′-aminophenyl)benzothiazole that led to successful tumor imaging. The results render the 2-(4′-aminophenyl) benzothiazole complexes potential candidates for imaging (99mTc) and targeted radiotherapy (188Re) of breast cancer.
- Tzanopoulou, Stamatia,Sagnou, Marina,Paravatou-Petsotas, Maria,Gourni, Eleni,Loudos, George,Xanthopoulos, Stavros,Lafkas, Daniel,Kiaris, Hippokratis,Varvarigou, Alexandra,Pirmettis, Ioannis C.,Papadopoulos, Minas,Pelecanou, Maria
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experimental part
p. 4633 - 4641
(2010/09/14)
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- Creating an antibacterial with in vivo efficacy: Synthesis and characterization of potent inhibitors of the bacterial cell division protein FTSZ with improved pharmaceutical properties
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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
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supporting information; experimental part
p. 3927 - 3936
(2010/09/04)
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- Synthesis and evaluation of18F-labeled 2-phenylbenzothiazoles as positron emission tomography imaging agents for amyloid plaques in alzheimer's disease
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Imaging agents targeting amyloid β(Aβ) may be useful for early diagnosis and follow-up of treatment of patients with Alzheimer's disease (AD). Three of five tested 2-(4′-fluorophenyl)-1,3-benzothiazoles displayed high binding affinities for Aβ plaques in
- Serdons, Kim,Terwinghe, Christelle,Vermaelen, Peter,Van Laere, Koen,Kung, Hank,Mortelmans, Luc,Bormans, Guy,Verbruggen, Alfons
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experimental part
p. 1428 - 1437
(2009/12/26)
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- 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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- 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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- Fused thiophene compounds and medicinal use thereof
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A condensed thiophene compound of the formula (I) wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof and hydrates thereof. The compound of the formula (I) of the present invention is useful as a novel antipsychotic agent which is effective for both positive symptoms and negative symptoms of schizophrenia, which is associated with less side effects such as extrapyramidal motor disorder and the like and which is less associated with serious side effects such as agranulocytosis and the like. In addition, this compound is also useful as a therapeutic agent of Alzheimer's disease and manic-depressive illness.
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- 3-carboalkoxy-2, 3-dihydro-1H-phenothiazin-4[10H]-one derivatives
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Phenothiazines of the formula: STR1 where R1 is H or --COOR, where R is selected from the group consisting of branched or unbranched alkyl groups containing from 1 to 4 carbon atoms, and where X is selected from H, branched or unbranched alkyl groups containing from 1 to 4 carbons, and halogen, and pharmaceutically acceptable salts thereof. Particularly preferred phenothiazines are those wherein X is hydrogen, chloro, bromo or methyl, R1 is COOR, and R is methyl, ethyl or t-butyl.
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- Highly selective aldose reductase inhibitors. II. Optimization of the aryl part of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids
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Accumulation of intracellular sorbitol, the product of glucose reduction catalyzed by aldose reductase (AR) [EC 1.1.1.21], is thought to be the main culprit in the development of diabetic complications. A series of 3- arylalkyl-2,4,5-trioxoimidazolidine-1-acetic acids was prepared and tested for inhibitory activities towards AR and aldehyde reductase (ALR) [EC 1.1.1.2]. These derivatives showed strong inhibitory activity against AR without markedly inhibiting ALR. In particular, the compounds with 3- nitrophenyl, 4-chloro-3-nitrophenyl, and chloro-substituted benzothiazolyl groups as the aryl part showed powerful AR-inhibitory activity. The chloro- substituted benzothiazolyl compound showed an AR selectivity of more than 5000 fold.
- Kotani, Takayuki,Ishii, Akira,Nagaki, Yasuhiro,Toyomaki, Yoshio,Yago, Hisashi,Suehiro, Seishi,Okukado, Nobuhisa,Okamoto, Kaoru
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p. 297 - 304
(2007/10/03)
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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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- 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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- Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-1 ,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position
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In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hyperte
- Yanagisawa,Fujimoto,Shimoji,Kanazaki,Mizutari,Nishino,Shiga,Koike
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p. 2055 - 2061
(2007/10/02)
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- Syntheses of 1,5-Benzothiazepines: Part III - Syntheses of 4-(p-Chlorophenyl)-2-(p-methoxyphenyl)-8-substituted-2,3-dihydro-1,5-benzothiazepines
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4-Methoxy-4'-chlorobenzalacetophenone (IV) on reaction with 5-substituted 2-aminothiophenols (IIIa-f) in toluene gives 4-(p-chlorophenyl)-2-(p-methoxyphenyl)-8-substituted-2,3-dihydro-1,5-benzothiazepines (Va-f).Their structures have been established by IR, PMR and mass spectral data.
- Pant, Umesh C.,Gaur, B. S.,Chugh, Manju
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p. 189 - 190
(2007/10/02)
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- THERMAL REARRANGEMENT OF O-THIOACYL DERIVATIVES OF N-ACYL-N-ARYLHYDROXYLAMINES
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The ability of the Ar-N-O-C=S system of atoms to undergo a thermal rearrangement of the Claisen type was investigated.On the basis of the experimental data it was concluded that the process is predominantly nonconcerted in nature.
- Drozd, V.N.
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p. 317 - 326
(2007/10/02)
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- A CONVENIENT AND SINGLE STEP SYNTHESIS OF SUBSTITUTED 4H-BENZOTHIAZINES.
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A simple one step synthesis is reported for substituted 4H-benzothiazines involving the condensation of 5-(chloro, bromo, methyl, methoxy, ethoxy)-, 4-methyl- and 3-(chloro and methoxy)-2-aminobenzenethiols with acetylacetone/ethyl acetoacetate/dibenzoylmethane in DMSO.
- Gupta, R. R.,Ojha, K. G.,Kalwania, G. S.,Kumar, M.
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p. 1145 - 1149
(2007/10/02)
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