Quinoxalin-2(1H)-one based design and synthesis produced several series of aldose reductase (ALR2) inhibitor candidates. In particular, phenolic structure was installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications. Most of the series 6 showed potent and selective effects on ALR2 inhibition with IC50 values in the range of 0.032-0.468 μM, and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active. More significantly, most of the series 8 revealed not only good activity in the ALR2 inhibition but also potent antioxidant activity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2-oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong as the well-known antioxidant Trolox at a concentration of 100 μM, verifying the C3 p-hydroxystyryl side chain as the key structure for alleviating oxidative stress. These results therefore suggest an achievement of multifunctional ALR2 inhibitors having both potency for ALR2 inhibition and as antioxidants.
Novel nitro-benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of them, 5-nitro and 8-nitro bearing ones displayed significant activity in IC50 values of 4.6 and 13.45µM. Their docking behaviors were also studied.
Previous works on emotion recognition in conversation (ERC) follow a two-step paradigm, which can be summarized as first producing context-independent features via fine-tuning pretrained language models (PLMs) and then analyzing contextual information and dialogue structure information among the extracted features. However, we discover that this paradigm has several limitations. Accordingly, we propose a novel paradigm, i.e., exploring contextual information and dialogue structure information in the fine-tuning step, and adapting the PLM to the ERC task in terms of input text, classification structure, and training strategy. Furthermore, we develop our model BERT-ERC according to the proposed paradigm, which improves ERC performance in three aspects, namely suggestive text, fine-grained classification module, and two-stage training. Compared to existing methods, BERT-ERC achieves substantial improvement on four datasets, indicating its effectiveness and generalization capability. Besides, we also set up the limited resources scenario and the online prediction scenario to approximate real-world scenarios. Extensive experiments demonstrate that the proposed paradigm significantly outperforms the previous one and can be adapted to various scenes.
ARIs for diabetes: A series of 2-(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid derivatives were designed and synthesized as inhibitors of aldose reductase (AR), a novel target for the treatment of diabetes complications. Most of the derivatives proved to be potent and selective, with IC50 values in the low nanomolar to micromolar range.
A copper catalyst system for the asymmetric 1,4-hydrosilylation of the α,β-unsaturated carboxylate class was developed by which synthesis of (+)- and (−)-enantiomers of 1,2-benzothiazine-1,1-dioxide acetates has been achieved with a good yield and an excellent level of enantioselectivity. A comparative structure–activity relationship study yielded the following order of aldose reductase inhibition activity: (−)-enantiomers > racemic > (+)-enantiomers. Further, a molecular docking study suggested that the (−)-enantiomer had significant binding affinity and thus increased inhibition activity.
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