Rational design and synthesis of potent and long-lasting glutamic acid-based dipeptidyl peptidase IV inhibitors.

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Tsai TY, Hsu T, Chen CT, Cheng JH, Chiou MC, Huang CH, Tseng YJ, Yeh TK, Huang CY, Yeh KC, Huang YW, Wu SH, Wang MH, Chen X, Chao YS, Jiaang WT

Rational design and synthesis of potent and long-lasting glutamic acid-based dipeptidyl peptidase IV inhibitors.

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1908-12. doi: 10.1016/j.bmcl.2009.02.061. Epub 2009 Feb 21.

PubMed ID

19269819 [ View in PubMed

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Abstract

A series of (2S)-cyanopyrrolidines with glutamic acid derivatives at the P2 site have been prepared and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV). The structure-activity relationships (SAR) led to the discovery of potent 3-substituted glutamic acid analogues, providing enhanced chemical stability and excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. Compound 13f exhibited the ability to both significantly decrease the glucose excursion and inhibit plasma DPP-IV activity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sitagliptin	Dipeptidyl peptidase 4	IC 50 (nM)	30	N/A	N/A	Details
Vildagliptin	Dipeptidyl peptidase 4	IC 50 (nM)	56	N/A	N/A	Details