27006-76-4Relevant articles and documents
Synthesis of novel EP4 antagonists and their use in cancer and inflammation
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Paragraph 0302; 0307-0312, (2021/09/08)
The present invention relates to a compound capable of effectively antagonizing EP4, which is a compound represented by formula I, or a tautomer, a stereoisomer, a hydrate, a solvate, a pharmaceutically-acceptable salt or a prodrug of the compound represented by formula I. R1 is selected from -CH3, -CHF2, and -CF3; R2 is selected from C2-C6 alkyl, C3-C6 cycloalkyl, halogenated C2-C6 alkyl, and halogenated C3-C6 cycloalkyl; R3 is selected from hydrogen, halogen, C1-C2 alkyl, and fluorinated C1-C2 alkyl; R4 is selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, and halogenated C1-C6 alkoxy.
Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: Pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment
Chen, Min,Li, Guohua,Lu, Aimin,Qiu, Lingling,Wang, An,Wang, Xiaobin,Xue, Wei,Yang, Chunlong
, p. 14426 - 14437 (2020/12/22)
The pyrazole-4-carboxamide scaffold containing a flexible amide chain has emerged as the molecular skeleton of highly efficient agricultural fungicides targeting succinate dehydrogenase (SDH). Based on the above vital structural features of succinate dehydrogenase inhibitors (SDHI), three types of novel pyrazole-4-formylhydrazine derivatives bearing a diphenyl ether moiety were rationally conceived under the guidance of a virtual docking comparison between bioactive molecules and SDH. Consistent with the virtual verification results of a molecular docking comparison, the in vitro antifungal bioassays indicated that the skeleton structure of title compounds should be optimized as an N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide scaffold. Strikingly, N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide derivatives 11o against Rhizoctonia solani, 11m against Fusarium graminearum, and 11g against Botrytis cinerea exhibited excellent antifungal effects, with corresponding EC50 values of 0.14, 0.27, and 0.52 μg/mL, which were obviously better than carbendazim against R. solani (0.34 μg/mL) and F. graminearum (0.57 μg/mL) as well as penthiopyrad against B. cinerea (0.83 μg/mL). The relative studies on an in vivo bioassay against R. solani, bioactive evaluation against SDH, and molecular docking were further explored to ascertain the practical value of compound 11o as a potential fungicide targeting SDH. The present work provided a non-negligible complement for the structural optimization of antifungal leads targeting SDH.
Design, synthesis, and biological evaluation of novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and ros in cancer cells
Xiong, Biao,Chen, Shi,Zhu, Peng,Huang, Meiling,Gao, Weijie,Zhu, Rui,Qian, Jianqiang,Peng, Yanfu,Zhang, Yanan,Dai, Hong,Ling, Yong
, p. 743 - 754 (2019/11/02)
Background: A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Objective: Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Methods: Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by1HNMR,13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Results: Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro, displaying potencies superior to 5-FU. In particular, the most potent compound 13l selectively inhibited proliferation of colorectal cancer HCT116 cells but not normal colon CCD841 cells. Furthermore, compound 13l also selectively promoted intracellular ROS accumulation in HCT116 which was involved in 13l inhibition of cancer cell proliferation and induction of cell apoptosis. Finally, compound 13l also dose-dependently induced cancer cell apoptosis by regulating apoptotic and DNA damage related proteins expressions. Conclusion: Our synthetic bis-pyrazole oxime derivatives possess potent antitumor activities by selectively inducing apoptosis and ROS accumulation in cancer cells, which may hold great promise as therapeutic agents for the treatment of human cancers.
