13183-79-4Relevant articles and documents
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.
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.
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.
