105-35-1Relevant articles and documents
Rational Design, Synthesis, and Biological Activity of N-(1,4-Benzoxazinone)Acetamide Derivatives as Potent Platelet Aggregation Inhibitors
Xiang, Yi,Wang, Xiu-Hua,Yang, Quan,Tan, Jia-Lian,Jang, Hee-Jae,Zuo, Hua,Shin, Dong-Soo
, p. 146 - 155 (2018)
Inappropriate thrombus formation within blood vessels is the leading cause of mortality in the industrialized world. Platelet aggregation activated by thrombin may have close relationship with thrombosis. Based on our studies on the pharmacophoric role of 1,4-benzoxazine-3(4H)-one for desirable platelet aggregation inhibitory activity, we identified N-(4-ethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2-(4-methylpiperazin-1-yl)acetamide (BOAP-AM6) and N-(4-butyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2-(4-(4-fluorophenyl)piperazin-1-yl)acetamide (BOAP-AM21) as platelet aggregation inhibitors with an IC50 of 8.93 and 8.67 μM, respectively, as potent as the positive control aspirin. A combination of structure–activity relationships studies and molecular modeling revealed that the molecule BOAP-AM6 interacted with the amino acid residue TYR166 and ARG214 in the binding site of GPIIb/IIIa receptor through hydrogen bond and compound BOAP-AM21 acted on the amino acid residue ASN215 and ALA218, both through the same approach as the reported potent molecules 7a and 7b.
Synthesis and acaricidal activities of scopoletin phenolic ether derivatives: Qsar, molecular docking study and in silico Adme predictions
Luo, Jinxiang,Lai, Ting,Guo, Tao,Chen, Fei,Zhang, Linli,Ding, Wei,Zhang, Yongqiang
, (2018/05/04)
Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR,1H-NMR,13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q2 = 0.802, r2 = 0.993; CoMSIA: q2 = 0.735, r2 = 0.965) results show that bulky substituents at R4, R1, R2 and R5 (C6, C3, C4, and C7) positions, electron positive groups at R5 (C7) position, hydrophobic groups at R1 (C3) and R2 (C4), H-bond donors groups at R1 (C3) and R4 (C6) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates.
Direct Catalytic Asymmetric Aldol Reaction of an α-Azido Amide
Weidner, Karin,Sun, Zhongdong,Kumagai, Naoya,Shibasaki, Masakatsu
supporting information, p. 6236 - 6240 (2015/05/20)
A direct aldol reaction of an α-azido 7-azaindolinylamide, promoted by a Cu-based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7-azaindolinylamide moiety furnished enantioenriched β-hydroxy-α-azido carboxylic acid derivatives.
