Xi:Irritant;27006-82-2Relevant academic research and scientific papers
Synthesis of novel EP4 antagonists and their use in cancer and inflammation
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Paragraph 0302; 0307; 0313-0317, (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, antifungal activity and 3D-QSAR study of novel pyrazole carboxamide and niacinamide derivatives containing benzimidazole moiety
Si, Wei-Jie,Wang, Xiao-Bin,Chen, Min,Wang, Meng-Qi,Lu, Ai-Min,Yang, Chun-Long
, p. 3000 - 3010 (2019/02/17)
A series of novel pyrazole carboxamide and niacinamide derivatives containing a benzimidazole moiety were designed and synthesized as antifungal candidate agents. All target compounds were characterized by FTIR, 1H NMR, 13C NMR, HRMS and elemental analysis techniques. The structure of compound T1 was further confirmed by single crystal X-ray diffraction analysis. The antifungal activities of the target compounds were evaluated in vitro against four phytopathogenic fungi (namely Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum and Alternaria solani) by the mycelium growth inhibition method. The bioassay results indicated that some of the compounds exhibited good antifungal activity against B. cinerea at 100 μg ML?1 compared to other three fungi. In order to better explore the structure-activity relationship (SAR), the EC50 values of target compounds against B. cinerea were measured and assessed. Subsequently, a 3D quantitative structure-activity relationship (3D-QSAR) study was carried out using the comparative molecular field analysis (CoMFA) technique based on the inhibitory activities of tested compounds against B. cinerea. Molecular modelling results revealed fine predictive ability with cross-validated q2 and non-cross-validated r2 values of 0.578 and 0.850, respectively.
Synthesis and bioactivity of pyrazole acyl thiourea derivatives
Wu, Jian,Shi, Qing,Chen, Zhuo,He, Ming,Jin, Linhong,Hu, Deyu
scheme or table, p. 5139 - 5150 (2012/07/03)
Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3- methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3- methyl -1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.
Synthesis and antiviral activity of novel pyrazole amides containing α-aminophosphonate moiety
Wu, Lintao,Song, Baoan,Bhadury, Pinaki S.,Yang, Song,Hu, Deyu,Jin, Linhong
scheme or table, p. 389 - 396 (2011/06/20)
A series of novel pyrazole amides J1-J15 containing an α-aminophosphonate moiety were synthesized and subsequently characterized by spectral (IR, 1H-, 13C-, 31P-, and 19F-NMR) data and elemental analysis. The racemic sample of J1 was further separated into its enantiomers under normal-phase condition on two immobilized polysaccharide-based chiral stationary phases (Chiralpak IA and Chiralpak IC). The synthesized compounds revealed certain degree of antiviral activity in the bioassay. The title compounds (J 3, J10, and J12) showed some curative activities (39.9%, 41.8%, 50.1%, respectively) against tobacco mosaic virus at 0.5 mg/mL.
