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Novel 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives as potent and selective aldose reductase inhibitors with antioxidant activity.

ABSTRACT: To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-b]pyrazin-4(3H)-yl) acetic acid (4k) was the most active with an IC50 value of 0.023?µM. Moreover, it was encouraging to find that some derivatives showed strong antioxidant activity, and among them, the phenolic 3,5-dihydroxyl compound 4l with 7-bromo in the core structure was proved to be the most potent, even comparable to that of the well-known antioxidant Trolox. Thus the results suggested success in the construction of potent and selective AKR1B1 inhibitors with antioxidant activity.

SUBMITTER: Hao X

PROVIDER: S-EPMC6711126 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Novel 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives as potent and selective aldose reductase inhibitors with antioxidant activity.

Hao Xin X Qi Gang G Ma Hongxing H Zhu Changjin C Han Zhongfei Z

Journal of enzyme inhibition and medicinal chemistry 20191201 1

To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-b]pyrazin-4(3H)-yl) acetic acid (4k) was the most active with an IC50 value of 0.023 µM. Moreover, it was encouraging to ...[more]

PMID: 31347930

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