Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors

作者：Jadav Pradip^*; Bahekar Rajesh; Shah Shailesh R; Patel Dipam; Joharapurkar Amit; Jain Mukul; Sairam Kalapatapu V V M; Singh Praveen Kumar

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(8): 1918-1922.

DOI：10.1016/j.bmcl.2014.03.009

• Aminomethyl-piperidones
• DPP-IV inhibitors
• Long-acting
• Selective
• Antidiabetic

A series of novel aminomethyl-piperidones were designed and evaluated as potential DPP-IV inhibitors. Optimized analogue 12v ((4S, 5S)-5-(aminomethyl)-1-(2-(benzo[d][1,3] dioxol-5-yl) ethyl)-4-(2,5-difluorophenyl) piperidin-2-one) showed excellent in vitro potency and selectivity for DPP-IV over other serine proteases. The lead compound 12v showed potent and long acting antihyperglycemic effects (in vivo), along with improved pharmacokinetic profile.

• 出版日期2014-4-15