13183-79-4Relevant articles and documents
Discovery of quinazoline derivatives as a novel class of potent and in vivo efficacious LSD1 inhibitors by drug repurposing
Li, Zhonghua,Li, Zhongrui,Ma, Jinlian,Miao, Jinxin,Qin, Tingting,Yang, Nian,Zhang, Xinhui,Zhang, Zhenqiang,Zhao, Taoqian,Zhao, Xuan
, (2021/08/19)
Histone lysine-specific demethylase 1 (LSD1) is an important epigenetic modulator, and is implicated in malignant transformation and tumor pathogenesis in different ways. Therefore, the inhibition of LSD1 provides an attractive therapeutic target for cancer therapy. Based on drug repurposing strategy, we screened our in-house chemical library toward LSD1, and found that the EGFR inhibitor erlotinib, an FDA-approved drug for lung cancer, possessed low potency against LSD1 (IC50 = 35.80 μM). Herein, we report our further medicinal chemistry effort to obtain a highly water-soluble erlotinib analog 5k (>100 mg/mL) with significantly enhanced inhibitory activity against LSD1 (IC50 = 0.69 μM) as well as higher specificity. In MGC-803 cells, 5k suppressed the demethylation of LSD1, indicating its cellular activity against the enzyme. In addition, 5k had a remarkable capacity to inhibit colony formation, suppress migration and induce apoptosis of MGC803 cells. Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.
Preparative Synthesis of 1,3-Dialkyltetrazolium-5-thiolates from 1-Alkyltetrazole-5-thiols
Araki, Shuki,Hirashita, Tsunehisa,Kurabayashi, Hideaki,Murakami, Suguru,Shoji, Takuo
, p. 2956 - 2961 (2022/02/07)
Mesoionic 1,3-dialkyltetrazolium-5-thiolates can be prepared in good yields by alkylation of 1-alkyltetrazole-5-thiols with secondary alcohols in concentrated sulfuric acid. The thiolates are transformed into the corresponding olates through S-alkylation followed by hydrolysis. The olates were found to be liquid at room temperature and to work effectively as polar solvents. The use of a smaller amount of sulfuric acid led to drastically different products; S-bridged dimers linked by 1,2-dimethylethylene were formed as the major products.
Antibiotic-improved cefmenoxime hydrochloride synthesis process
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Paragraph 0039-0041, (2021/02/06)
The invention discloses an antibiotic-improved cefmenoxime hydrochloride synthesis process, which comprises the following steps: step 1, preparation of 1-methyl-5-sulfydryl-1H-tetrazole, step 2, preparation of 2-(2-amino-4-azolyl)-2(Z)-methoxyimino ethyl acetate; step 3, preparation of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid; step 4, preparation of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid-2-benzothiazole thioester; step 5, preparation of 7-amino-3-(1-methyl-1H-tetrazole-5-thiomethyl)cephalosporanic acid hydrochloride (7-ACA-MMT. HC1); and step 6, preparation of cefmenoxime hydrochloride; domestic raw materials are adopted, the raw materials are cheap and easy to obtain in the synthesis route, the synthesis cost is reduced, and synthesis is improved; the improved process has the advantages of low raw material cost, simplicity in operation and suitability for industrial production.
Preparation process of 5-mercapto-1-methyltetrazole
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Paragraph 0032-0041, (2020/06/09)
The invention relates to a preparation process of 5-mercapto-1-methyltetrazole, and belongs to the technical field of synthesis of medical intermediates. According to the preparation process, sodium azide and methyl isothiocyanate are used as raw materials, a cyclization reaction is carried out under the action of microwaves, a reaction product is directly cooled and separated out, and a 5-mercapto-1-methyltetrazole crude product is obtained after treatment. The preparation process is scientific and reasonable in design, effectively solves the problems of environmental protection and safety, reduces the cost, improves the productivity and is beneficial to industrial production.
Synthesis method of 1-methyl-5-mercaptotetrazole
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Paragraph 0018; 0020-0029, (2020/12/30)
The invention relates to a synthesis method of 1-methyl-5-mercaptotetrazole. The method comprises the following steps: (1) carrying out reflux reaction by using sodium methylamino dithiocarboxylate and sodium azide as reaction raw materials, water as a reaction solvent and an alkaline solution as a catalyst, neutralizing the reaction solution with a protonic acid after the reaction until the pH value is 6-7, and filtering to obtain a 1-methyl-5-mercaptotetrazole crude product; and (2) recrystallizing the 1-methyl-5-mercaptotetrazole crude product obtained in step (1) by using a recrystallization solution to obtain the 1-methyl-5-mercaptotetrazole finished product, wherein the recrystallization solution is a mixed solution of toluene and water. The synthesis method disclosed by the invention is high in yield, and the prepared 1-methyl-5-mercaptotetrazole is high in purity.
Preparation method of 5-mercapto-1H-tetrazole compound
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Paragraph 0025; 0027-0033, (2019/11/04)
The invention relates to a preparation method of a 5-mercapto-1H-tetrazole compound shown in a formula (III), which comprises the following steps of: (1) dissolving disulfide in halogenated alkane, dropwise adding a chlorinating reagent at -5 to 0 DEG C, carrying out heat preservation reaction for 2-5 hours, and carrying out reduced pressure distillation at 5-10 DEG C to obtain chlorinated disulfide; (2) dissolving the chlorinated disulfide prepared in the step (1) in lower saturated monohydric alcohol, dissolving sodium azide in water, dripping a sodium azide solution at 20-30 DEG C, heatingto 50-65 DEG C after dripping, and carrying out heat preservation reaction for 2-5 hours; (3) evaporating the solution obtained in the step (2) at 40-45 DEG C under reduced pressure to remove the lower saturated monohydric alcohol, and adding halogenated alkane for extraction for three times to obtain a halogenated alkane extraction liquid; (4) concentrating and crystallizing the halogenated alkane extraction liquid prepared in the step (3), and filtering to obtain the 5-mercapto-1H-tetrazole compound. The preparation method has high yield, good product quality, convenient solvent recycling and low production cost.
NOVEL CRYSTALLINE CEFOPERAZONE INTERMEDIATE
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Paragraph 0061, (2015/04/28)
The present invention relates to a crystalline form of an intermediate for cefoperazone of formula (1) and to a process for the preparation thereof by enzymatic condensation of a 3′-thiosubstituted β-lactam nucleus with a phenylglycine derivative.
Improved efficiency of CdS quantum dot sensitized solar cell with an organic redox couple and a polymer counter electrode
Shu, Ting,Li, Xiong,Ku, Zhi-Liang,Wang, Shi,Wu, Shi,Jin, Xiao-Hong,Hu, Chun-Di
, p. 700 - 704 (2014/12/11)
Quantum dot sensitized solar cells (QDSSCs) based on an organic thiolate/disulfide redox couple (C7H5N4S-/C14H10N8S2or C2H3N4S-/C4H6N8S2) and a polymer counter electrode [poly (3, 4-ethylenedioxythiophene), PEDOT] were fabricated and their photovoltaic performance were investigated. In CdS QDSSC, the organic C7H5N4S-/C14H10N8S2electrolyte shows better performance than the polysulfide electrolyte, and the PEDOT counter electrode exhibits higher efficiency than that of the Pt counter electrode and the CoS counter electrode. An efficiency of 1.53% was achieved in this QDSSC. The influences of the morphology and the deposition charge of the PEDOT counter electrodes on the cell performance were also studied. Furthermore, it was found that the C7H5N4S-/C14H10N8S2redox couple outperformed the C2H3N4S-/C4H6N8S2redox couple due to reduced electron recombination.
Synthesis and biological properties of new 1β-methylcarbapenems having tetrazolothioether moiety
Shin, Kye Jung,Koo, Ki Dong,Yoo, Kyung Ho,Kim, Dong Chan,Kim, Dong Jin,Park, Sang Woo
, p. 1421 - 1425 (2007/10/03)
The synthesis and biological activities of a series of new 1β-methylcarbapenems 1a-1 having tetrazolothioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1c showed the most potent antibacterial activity and advanced pharmacokinetics compared with imipenem and meropenem. (C) 2000 Elsevier Science Ltd. All rights reserved.
Precious metal composition
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, (2008/06/13)
Gold thiolates of formula AuSR'' or a salt thereof, in which R'' is such that HSR'' represents: 4,6-dihydroxy-2-mercaptopyrimidine; N-(2-mercaptoacetyl)glycine; N-(3-mercaptopropionyl)glycine; and N-(2-mercaptopropionyl)glycine. The invention provides also processes for preparing novel gold thiolates.
