14062-34-1Relevant articles and documents
Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
, (2021/03/24)
Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Paragraph 0445, (2020/01/02)
The present disclosure relates to a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.
N-(5-Methyl-1,3-Thiazol-2-yl)-2-{[5-((Un)Substituted- Phenyl)1,3,4-Oxadiazol-2-yl]Sulfanyl}acetamides. Unique Biheterocycles as Promising Therapeutic Agents
Abbasi,Ramzan,Aziz-ur-Rehman,Siddiqui,Shah,Hassan,Seo,Ashraf,Mirza,Ismail
, p. 801 - 811 (2019/02/27)
An electrophile, 2-bromo-N-(5-methyl-1,3-thiazol-2-yl)acetamide, was synthesized by the reaction of 5-methyl-1,3-thiazol-2-amine and bromoacetyl bromide in an aqueous medium. In a parallel scheme, a series of (un)substituted benzoic acids was converted sequentially into respective esters, acid hydrazides, and then into 1,3,4-oxadiazole heterocyclic cores. The electrophile was coupled with the aforementioned 1,3,4-oxadiazoles to obtain the targeted bi-heterocyles. Structural analysis of the synthesized compounds was performed by IR, EI-MS, 1H NMR, and 13C NMR. The enzyme inhibition study of these molecules was carried out against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, α-glucosidase, and urease. The interactions of these compounds with respective enzymes were recognized by their in silico study. Moreover, their cytotoxicity was also determined to find out their utility as possible therapeutic agents.
