Synthesis and biological evaluation of triazepane derivatives as DPP-IV inhibitors

A series of triazepane derivatives such as (R)-3-amino-1-(1,2,5-triazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-ones (7, 13a–p) and (R)-3-amino-1-(1,2,5-triazepan-5-yl)-4-(2,4,5-trifluorophenyl)butan-1-ones (17a–e) was synthesized and evaluated for their ability to inhibit dipeptidyl peptidase IV (DPP-IV) enzyme. Compounds with the acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. Among them, compound 13p ((R)-4-[1-acetyl-2-{3-amino-4-(2,4,5-trifluorophenyl)butanoyl-1,2,5-triazepan-5-carbonyl}benzoic acid]) showed a good in vitro activity without inhibiting CYP.

Graphical abstractA series of triazepane derivatives such as (R)-3-amino-1-(1,2,5-triazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-ones (7, 13a–p) and (R)-3-amino-1-(1,2,5-triazepan-5-yl)-4-(2,4,5-trifluorophenyl)butan-1-ones (17a–e) was synthesized and evaluated for their ability to inhibit the dipeptidyl peptidase IV (DPP-IV) enzyme. Compounds with the acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. Among them, compound 13p ((R)-4-[1-acetyl-2-{3-amino-4-(2,4,5-trifluorophenyl)butanoyl-1,2,5-triazepan-5-carbonyl}-benzoic acid]) showed a good in vitro activity without inhibiting CYP.Figure optionsDownload full-size imageDownload as PowerPoint slide