Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

Na Luo; Xiaoyu Fang; Mingbo Su; Xinwen Zhang; Dan Li; Honglin Li; Shiliang Li; Zhenjiang Zhao

doi:10.1002/cjoc.202000342

Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

Na Luo
, Xiaoyu Fang
, Mingbo Su
, Xinwen Zhang
, Dan Li
, Honglin Li
, Shiliang Li^*
, Zhenjiang Zhao^*

^*Corresponding author for this work

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

4 Scopus citations

Abstract

Dipeptidyl peptidase 4 (DPP-4) is a clinically validated target for the treatment of type 2 diabetes mellitus (T2DM). To discover novel and potent DPP-4 inhibitors, three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine. Among the designed compounds, 41d-1 was the most potent one with an IC₅₀ value of 16.00 nM. Besides, 41d-1 (5 mg/kg) displayed a moderate glucose tolerance capability in ICR mice. Structure-activity-relationship (SAR) studies were discussed in detail, which is constructive for our further optimization.

Original language	English
Pages (from-to)	115-120
Number of pages	6
Journal	Chinese Journal of Chemistry
Volume	39
Issue number	1
DOIs	https://doi.org/10.1002/cjoc.202000342
State	Published - Jan 2021
Externally published	Yes

Keywords

Dipeptidyl peptidase IV
Inhibitors
Molecular docking
Structure-activity relationship
Type II diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cjoc.202000342

Cite this

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title = "Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors",

abstract = "Dipeptidyl peptidase 4 (DPP-4) is a clinically validated target for the treatment of type 2 diabetes mellitus (T2DM). To discover novel and potent DPP-4 inhibitors, three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine. Among the designed compounds, 41d-1 was the most potent one with an IC50 value of 16.00 nM. Besides, 41d-1 (5 mg/kg) displayed a moderate glucose tolerance capability in ICR mice. Structure-activity-relationship (SAR) studies were discussed in detail, which is constructive for our further optimization.",

keywords = "Dipeptidyl peptidase IV, Inhibitors, Molecular docking, Structure-activity relationship, Type II diabetes",

author = "Na Luo and Xiaoyu Fang and Mingbo Su and Xinwen Zhang and Dan Li and Honglin Li and Shiliang Li and Zhenjiang Zhao",

note = "Publisher Copyright: {\textcopyright} 2020 SIOC, CAS, Shanghai \& WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim",

year = "2021",

month = jan,

doi = "10.1002/cjoc.202000342",

language = "英语",

volume = "39",

pages = "115--120",

journal = "Chinese Journal of Chemistry",

issn = "1001-604X",

publisher = "John Wiley and Sons Inc",

number = "1",

}

TY - JOUR

T1 - Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

AU - Luo, Na

AU - Fang, Xiaoyu

AU - Su, Mingbo

AU - Zhang, Xinwen

AU - Li, Dan

AU - Li, Honglin

AU - Li, Shiliang

AU - Zhao, Zhenjiang

PY - 2021/1

Y1 - 2021/1

N2 - Dipeptidyl peptidase 4 (DPP-4) is a clinically validated target for the treatment of type 2 diabetes mellitus (T2DM). To discover novel and potent DPP-4 inhibitors, three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine. Among the designed compounds, 41d-1 was the most potent one with an IC50 value of 16.00 nM. Besides, 41d-1 (5 mg/kg) displayed a moderate glucose tolerance capability in ICR mice. Structure-activity-relationship (SAR) studies were discussed in detail, which is constructive for our further optimization.

AB - Dipeptidyl peptidase 4 (DPP-4) is a clinically validated target for the treatment of type 2 diabetes mellitus (T2DM). To discover novel and potent DPP-4 inhibitors, three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine. Among the designed compounds, 41d-1 was the most potent one with an IC50 value of 16.00 nM. Besides, 41d-1 (5 mg/kg) displayed a moderate glucose tolerance capability in ICR mice. Structure-activity-relationship (SAR) studies were discussed in detail, which is constructive for our further optimization.

KW - Dipeptidyl peptidase IV

KW - Inhibitors

KW - Molecular docking

KW - Structure-activity relationship

KW - Type II diabetes

UR - https://www.scopus.com/pages/publications/85097986895

U2 - 10.1002/cjoc.202000342

DO - 10.1002/cjoc.202000342

M3 - 文章

AN - SCOPUS:85097986895

SN - 1001-604X

VL - 39

SP - 115

EP - 120

JO - Chinese Journal of Chemistry

JF - Chinese Journal of Chemistry

IS - 1

ER -

Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

Abstract

Keywords

UN SDGs

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