Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold

Xin Chen; Yanchun Yang; Bing Ma; Shuzhen Zhang; Minlan He; Dequan Gui; Saghir Hussain; Chaojun Jing; Changjin Zhu; Qun Yu; Yan Liu

doi:10.1016/j.ejmech.2011.01.072

Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold

Xin Chen, Yanchun Yang, Bing Ma, Shuzhen Zhang, Minlan He, Dequan Gui, Saghir Hussain, Chaojun Jing, Changjin Zhu^*, Qun Yu, Yan Liu

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC₅₀ values ranging from 0.038 μM to 11.29 μM. Most but not all of them showed a strong ALR2 inhibition activity and significant selectivity, which were further supported by docking studies. Of these inhibitors, compound 7d exhibited highest inhibition activity. Structure-activity relationship studies indicate the requirement of N2-benzyl group with electron-withdrawing substituents and N4-acetic acid group in the pyridothiadiazine scaffold.

Original language	English
Pages (from-to)	1536-1544
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	5
DOIs	https://doi.org/10.1016/j.ejmech.2011.01.072
Publication status	Published - May 2011

Keywords

Acetic acid derivative
Aldose reductase
Inhibitor
Pyrido[2,3e]-[1,2,4]-thiadiazine

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10.1016/j.ejmech.2011.01.072

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title = "Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold",

abstract = "A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.038 μM to 11.29 μM. Most but not all of them showed a strong ALR2 inhibition activity and significant selectivity, which were further supported by docking studies. Of these inhibitors, compound 7d exhibited highest inhibition activity. Structure-activity relationship studies indicate the requirement of N2-benzyl group with electron-withdrawing substituents and N4-acetic acid group in the pyridothiadiazine scaffold.",

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author = "Xin Chen and Yanchun Yang and Bing Ma and Shuzhen Zhang and Minlan He and Dequan Gui and Saghir Hussain and Chaojun Jing and Changjin Zhu and Qun Yu and Yan Liu",

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doi = "10.1016/j.ejmech.2011.01.072",

language = "English",

volume = "46",

pages = "1536--1544",

journal = "European Journal of Medicinal Chemistry",

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TY - JOUR

T1 - Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold

AU - Chen, Xin

AU - Yang, Yanchun

AU - Ma, Bing

AU - Zhang, Shuzhen

AU - He, Minlan

AU - Gui, Dequan

AU - Hussain, Saghir

AU - Jing, Chaojun

AU - Zhu, Changjin

AU - Yu, Qun

AU - Liu, Yan

PY - 2011/5

Y1 - 2011/5

N2 - A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.038 μM to 11.29 μM. Most but not all of them showed a strong ALR2 inhibition activity and significant selectivity, which were further supported by docking studies. Of these inhibitors, compound 7d exhibited highest inhibition activity. Structure-activity relationship studies indicate the requirement of N2-benzyl group with electron-withdrawing substituents and N4-acetic acid group in the pyridothiadiazine scaffold.

AB - A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.038 μM to 11.29 μM. Most but not all of them showed a strong ALR2 inhibition activity and significant selectivity, which were further supported by docking studies. Of these inhibitors, compound 7d exhibited highest inhibition activity. Structure-activity relationship studies indicate the requirement of N2-benzyl group with electron-withdrawing substituents and N4-acetic acid group in the pyridothiadiazine scaffold.

KW - Acetic acid derivative

KW - Aldose reductase

KW - Inhibitor

KW - Pyrido[2,3e]-[1,2,4]-thiadiazine

UR - http://www.scopus.com/inward/record.url?scp=79953226757&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2011.01.072

DO - 10.1016/j.ejmech.2011.01.072

M3 - Article

C2 - 21367494

AN - SCOPUS:79953226757

SN - 0223-5234

VL - 46

SP - 1536

EP - 1544

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 5

ER -

Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold

Abstract

Keywords

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