Xn:Harmful;3622-04-6Relevant articles and documents
N-Arylalkylbenzo[d]thiazole-2-carboxamides as anti-mycobacterial agents: Design, new methods of synthesis and biological evaluation
Shah, Parth,Dhameliya, Tejas M.,Bansal, Rohit,Nautiyal, Manesh,Kommi, Damodara N.,Jadhavar, Pradeep S.,Sridevi, Jonnalagadda Padma,Yogeeswari, Perumal,Sriram, Dharmarajan,Chakraborti, Asit K.
, p. 1489 - 1495 (2014)
Benzothiazole-2-carboxyarylalkylamides are reported as a new class of potent anti-mycobacterial agents. Forty-one target compounds have been synthesized following a green synthetic strategy using water as the reaction medium to construct the benzothiazole scaffold followed by (i) microwave-assisted catalyst-free and (ii) ammonium chloride-catalyzed solvent-free amide coupling. The anti-mycobacterial potency of the compounds was determined against H37Rv strain. Twelve compounds exhibited promising anti-TB activity in the range of 0.78-6.25 μg mL-1 and were found to be non-toxic (-1) to HEK 293T cell lines with therapeutic index (TI) of 8-64. The most promising anti-TB compound 5bf showed MIC of 0.78 μg mL-1 (TI > 64). The molecular docking studies of 5bf predict it to be a ligand for the M. tuberculosis HisG, the putative drug target for tuberculosis and could serve as a guiding principle for lead optimization.
Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents
Zhao, Liyu,Sun, Yin,Yin, Wenbo,Tian, Linfeng,Sun, Nannan,Zheng, Yang,Zhang, Chu,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
, (2021/11/22)
To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.
6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects**
Akins, Nicholas S.,Ashpole, Nicole M.,Dudhipala, Narendar,Harris, Hannah M.,Keasling, Adam W.,Kim, Seong Jong,Le, Hoang V.,Majumdar, Soumyajit,Mishra, Nisha,Paris, Jason J.,Zjawiony, Jordan K.
, (2022/02/17)
Current common analgesics are mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. However, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that many of these compounds have dual agonism on kappa and mu opioid receptors. In vivo studies on the lead dual kappa and mu opioid receptor agonist demonstrated supraspinal thermal analgesic activity while avoiding anxiogenic effects in male mice, thus providing further strong evidence in support of the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.
PRODUCTION METHOD OF BENZOTHIAZOLE DERIVATIVE
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, (2020/06/18)
PROBLEM TO BE SOLVED: To provide: a production method of a benzothiazole derivative; as well as a production method of a polymerizable compound produced from the benzothiazole derivative; a polymerizable composition including the polymerizable compound; a polymer obtained by polymerizing the polymerizable composition; and an optical isomer utilizing the polymer. SOLUTION: A production method of a compound represented by the following general formula (III) is provided, and also a production method of a polymerizable compound produced from the compound represented by the general formula (III), a polymerizable composition, a polymer obtained by polymerizing the polymerizable composition, and an optical isomer utilizing the polymer are provided. When the polymerizable composition containing the compound is polymerized and the obtained film-like polymer is irradiated with ultraviolet light, change of color and change of phase difference scarcely take place. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
MANUFACTURING INTERMEDIATE AND MANUFACTURING METHOD OF POLYMERIZABLE COMPOUND
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Paragraph 0172; 0175; 0189-0190, (2020/04/09)
PROBLEM TO BE SOLVED: To provide a manufacturing intermediate hardly generating discoloration and change of haze, when ultraviolet is radiated to a film-shaped polymer obtained by manufacturing a polymerizable compound and polymerizing a polymerizable composition containing the compound, and a manufacturing method of the manufacturing intermediate. SOLUTION: There are provided a compound represented by the formula (II), a manufacturing method of the compound, a polymerizable compound manufactured from the compound, a polymerizable composition, a polymer obtained by polymerizing the polymerizable composition, and an optical isomer using the polymer. In the formula, R1, R2 and L1 represent organic groups, n1 represents an integer of 1 to 4, when a plurality of L1 exist, it may be same or different, and neighboring L1 each other may form a condensed ring. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Benzothiazole diazole derivative and preparation method and application thereof
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, (2019/04/26)
The invention belongs to the field of drug synthesis, and particularly relates to a benzothiazole diazole derivative and a preparation method thereof. The invention further relates to application of the diazole derivative in preparing drugs for treating various diseases caused by fungal infection or bacterial infection. The compound defined by the method is high in anti-fungal and anti-bacterial activity, compared with an existing anti-bacterial drug, the benzothiazole diazole derivative has the advantages of being novel in structure, efficient, broad in spectrum and the like, and therefore, the compound has a wide application prospect.
Thiazole carboxamide compound and synthesis and application thereof
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, (2019/04/26)
The invention relates to a novel thiazole carboxamide compound. R1, R2, Z, X1, X2, X3, n and m have meanings defined in right claims. The compound has a main inhibiting effect on alpha-glucosidase inhibitor, and can be used for preventing or treating dise
Structure-activity relationships of thiazole and benzothiazole derivatives as selective cannabinoid CB2 agonists with in vivo anti-inflammatory properties
Ghonim, Aya E.,Ligresti, Alessia,Rabbito, Alessandro,Mahmoud, Ali Mokhtar,Di Marzo, Vincenzo,Osman, Noha A.,Abadi, Ashraf H.
, p. 154 - 170 (2019/07/12)
The strong therapeutic potential of CB2 receptor agonists for use as anti-inflammatory agents that lack psychiatric side effects has attracted substantial interest. We herein describe the rational design and synthesis of novel thiazole and benzothiazole derivatives and the evaluation of their binding affinity and functional activity on CB1 and CB2 receptors. The series with the general formula N-(3-pentylbenzo [d]thiazol-2(3H)-ylidene) carboxamide (compounds 6a-6d) exhibited the highest affinity and selectivity towards CB2 receptors with Kis in the picomolar or low nanomolar range, and selectivity indices (Ki hCB1/Ki hCB2) reaching up to 429 fold. Notably, these compounds also demonstrated an agonistic functional activity in cellular assays with EC50s in the low nanomolar range. More interestingly, compound 6d, the 3-(trifluoromethyl)benzamide derivative, exhibited remarkable protection against DSS-induced acute colitis in mice model.
Benzo[d]thiazole-2-carbanilides as new anti-TB chemotypes: Design, synthesis, biological evaluation, and structure-activity relationship
Dhameliya, Tejas M.,Tiwari, Rishu,Banerjee, Arkaprabha,Pancholia, Sahaj,Sriram, Dharmarajan,Panda, Dulal,Chakraborti, Asit K.
, p. 364 - 380 (2018/06/14)
Tuberculosis is the second leading cause of deaths worldwide. The inadequacy of existing drugs to treat TB due to developed resistance and TB-HIV synergism urges for new anti-TB drugs. Seventy-two benzo[d]thiazole-2-carbanilides have been synthesized through CDI-mediated direct coupling of benzo[d]thiazole-2-carboxylic acids with aromatic amines using a three step methodology which includes a green protocol for synthesis of ethyl benzo[d]thiazole-2-carboxylates, precursor of the desired carboxylic acids. The compounds were evaluated in vitro for anti-tubercular activity against M. tuberculosis H37Rv (ATCC27294 strain). Thirty-two compounds exhibiting MIC values in the range of 0.78–6.25 μg/mL (1.9–23 μM) were subjected to cell viability test against RAW 264.7 cell lines and thirty compounds were found to be non-toxic (50% inhibition). The most active compounds with MIC of 0.78 μg/mL (e.g., 4i, 4n, 4s, 4w, 6f, 6h, 6u, 7e, 7h, 7p, 7r and 7w) exhibit therapeutic index of 64. The structure activity relationship of the N-arylbenzo[d]thiazole-2-carboxamides has been established for anti-mycobacterial activity. Molecular docking suggests that the compounds 7w, 4i and 4n bind to the catalytic site of the enzyme ATP Phosphoribosyltransferase (HisG) and might be attributed to their anti-TB potential. These can serve as a new starting point for the development of anti-TB agents with therapeutic potential.
A benzothiazole - 2 - carboxylic acid
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Paragraph 0034; 0036; 0038; 0040; 0042; 0044; 0092; 0093, (2017/08/25)
The invention relates to a preparation method of benzothiazole-2-carboxylic acid, and relates to the technical field of benzothiazole-2-carboxylic acid. According to the method, 2-methylbenzothiazole is adopted as a raw material; water and ethanol are adopted as a solvent, wherein the contents of water and ethanol are respectively 0-80% and 20-100%; 10-200ppm of mononuclear metalloporphyrin with a structure represented by the formula (I) or (II) is adopted as a catalyst; sodium hydroxide with a concentration of 0.5-2mol/L is adopted as an auxiliary agent; 0.5-2.0MPa oxygen and 30% hydrogen peroxide are adopted as oxidants; and a reaction is carried out for 2-12h under a temperature of 40-140 DEG C, such that benzothiazole-2-carboxylic acid is obtained. According to the invention, metalloporphyrin is adopted as the catalyst, such that dose is low, and pollution is prevented. Ethanol or an alkali solution of an ethanol and water mixed system is adopted as the solvent, such that the solvent is green, nontoxic and environment-friendly. Oxygen and hydrogen peroxide are adopted as oxidants, such that equipment corrosion caused by potassium permanganate and concentrated sulfuric acid is greatly reduced, and experimental operation safety and environment-friendliness are greatly improved.
