Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐(S)‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors

Lei Zhang; Mingbo Su; Jingya Li; Xun Ji; Jiang Wang; Zeng Li; Jia Li; Hong Liu

doi:10.1111/cbdd.12058

journal article Nov 19, 2012

Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐(S)‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors

Lei Zhang

Mingbo Su Jingya Li

Xun Ji Jiang Wang

Zeng Li

Jia Li

Hong Liu

Chemical Biology & Drug Design Vol. 81 No. 2 pp. 198-207 · Wiley

View at Publisher Save 10.1111/cbdd.12058

Abstract

Dipeptidyl peptidase‐4 inhibitors hold great potential for the treatment of type 2 diabetes. A series of 1‐(γ‐1,2,3‐triazol substituted prolyl)‐(S)‐3,3‐difluoropyrrolidines were designed, synthesized, and evaluated as novel dipeptidyl peptidase‐4 inhibitors. Most of the compounds exhibited good in vitro potency against dipeptidyl peptidase‐4. Among these, compounds 7j, 7q, and 7s displayed good dipeptidyl peptidase‐4 activity and excellent selectivity versus other proteases including dipeptidyl peptidase‐8, dipeptidyl peptidase‐9, and FAP. The possible binding modes of compounds 7j, 7q, and 7s with dipeptidyl peptidase‐4 were also explored by molecular docking simulation.

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References

25

[1]

10.1016/s0140-6736(11)60207-9

[2]

10.1124/pr.108.000604

[3]

The Physiology of Glucagon-like Peptide 1

Jens Juul Holst

Physiological Reviews 10.1152/physrev.00034.2006

[4]

10.1016/j.mce.2008.08.012

[5]

10.1111/j.1432-1033.1993.tb17986.x

[6]

10.1210/endo.136.8.7628397

[7]

10.1016/j.bmcl.2007.03.095

[8]

10.1185/030079908x261069

[9]

10.1517/14656566.2011.593508

[10]

10.1021/jm030091l

[11]

10.1021/jm050261p

[12]

10.1021/jm070104l

[13]

10.1021/jm701280z

[14]

10.2174/0929867053507298

[15]

10.1016/j.bmc.2009.01.061

[16]

10.1016/0960-894x(96)00190-4

[17]

10.2174/092986712803414213

[18]

10.2174/092986711796391615

[19]

10.2174/138955711793564051

[20]

10.3109/14756360903524304

[21]

10.1002/asia.201100432

[22]

10.2337/diabetes.54.10.2988

[23]

10.1016/s1046-5928(02)00043-8

[24]

10.1016/j.bmcl.2009.02.041

[25]

Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy

Richard A. Friesner, Jay L. Banks, Robert B. Murphy et al.

Journal of Medicinal Chemistry 10.1021/jm0306430

Metrics

10

Citations

25

References

Details

Published: Nov 19, 2012
Vol/Issue: 81(2)
Pages: 198-207
License: View

Authors

L

Lei Zhang

Northern Illinois University

Hefei University of Technology

Southwest University

Tianjin University of Technology

Cite This Article

Lei Zhang, Mingbo Su, Jingya Li, et al. (2012). Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐(S)‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors. Chemical Biology & Drug Design, 81(2), 198-207. https://doi.org/10.1111/cbdd.12058

Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐(S)‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors

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