Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors

Yang Liu; Meimei Si; Li Tang; Shihao Shangguan; Haoshu Wu; Jia Li; Peng Wu; Xiaodong Ma; Tao Liu; Yongzhou Hu

doi:10.1016/j.bmc.2013.07.034

Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors

Yang Liu, Meimei Si, Li Tang, Shihao Shangguan, Haoshu Wu, Jia Li, Peng Wu, Xiaodong Ma, Tao Liu, Yongzhou Hu

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79–25.52nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner.

Original language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	21
Issue number	18
Pages (from-to)	5679-5687
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2013.07.034
Publication status	Published - 2013
Externally published	Yes

Keywords

Dipeptidyl peptidase 4 inhibitors
Type 2 diabetes
1,2,3-Triazole
(S)-Phenylalanine derivatives
Selectivity

UN SDGs

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

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10.1016/j.bmc.2013.07.034

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title = "Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors",

abstract = "A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79–25.52nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner.",

keywords = "Dipeptidyl peptidase 4 inhibitors, Type 2 diabetes, 1,2,3-Triazole, (S)-Phenylalanine derivatives, Selectivity",

author = "Yang Liu and Meimei Si and Li Tang and Shihao Shangguan and Haoshu Wu and Jia Li and Peng Wu and Xiaodong Ma and Tao Liu and Yongzhou Hu",

year = "2013",

doi = "10.1016/j.bmc.2013.07.034",

language = "English",

volume = "21",

pages = "5679--5687",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

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TY - JOUR

T1 - Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors

AU - Liu, Yang

AU - Si, Meimei

AU - Tang, Li

AU - Shangguan, Shihao

AU - Wu, Haoshu

AU - Li, Jia

AU - Wu, Peng

AU - Ma, Xiaodong

AU - Liu, Tao

AU - Hu, Yongzhou

PY - 2013

Y1 - 2013

N2 - A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79–25.52nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner.

AB - A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79–25.52nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner.

KW - Dipeptidyl peptidase 4 inhibitors

KW - Type 2 diabetes

KW - 1,2,3-Triazole

KW - (S)-Phenylalanine derivatives

KW - Selectivity

U2 - 10.1016/j.bmc.2013.07.034

DO - 10.1016/j.bmc.2013.07.034

M3 - Journal article

C2 - 23938053

SN - 0968-0896

VL - 21

SP - 5679

EP - 5687

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 18

ER -

Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors

Abstract

Keywords

UN SDGs

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