Abstract
Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent.
Original language | English |
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Pages (from-to) | 1274-1279 |
Number of pages | 6 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 17 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2007 Mar 1 |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry