85862-68-6Relevant articles and documents
Quinazoline substituted 1, 2, 3-triazole derivative as well as pharmaceutical composition, preparation method and application thereof
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Paragraph 0068-0072, (2022/03/31)
The invention discloses a quinazoline substituted 1, 2, 3-triazole derivative, the derivative is shown as a general formula (I), and the definition of each substituent group is shown in the specification. In addition, the invention also discloses a preparation method of the compound. The compound shown in the general formula (I) has an inhibiting effect on proliferation of tumor cells, also has an inhibiting effect on proliferation of human colon cancer (HCT-116) and human lung cancer cell strain (A549) cells, and can be used as an antitumor drug.
Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors
Huang, Ming-Jie,Guo, Jia-Wen,Fu, Yun-Dong,You, Ya-Zhen,Xu, Wen-Yu,Song, Ting-Yu,Li, Ran,Chen, Zi-Tong,Huang, Li-Hua,Liu, Hong-Min
supporting information, (2021/04/12)
Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study
Assun??o, Elvis L. F.,Carvalho, Diego B.,das Neves, Amarith R.,Kawasoko Shiguemotto, Cristiane Y.,Portapilla, Gisele B.,de Albuquerque, Sergio,Baroni, Adriano C. M.
, p. 2019 - 2028 (2020/09/21)
Chagas disease affects 6–8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50=3.0 μM, SI>65.3), with an IC50=3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3?Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2, 4-CH3?Ph) with IC50=1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.