Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV

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• 作者：Takashi Kondo ; Isamu Sugimoto ; Takahiro Nekado ; Kenya Ochi ; Tazumi Ohtani ; Yohei Tajima ; Susumu Yamamoto ; Kazuhito Kawabata ; Hisao Nakai ; Masaaki Toda
• 关键词：DPP-IV inhibitor ; Prolylprolinenitriles ; Glucuronate
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 出版时间：1 April 2007
• 年：2007
• 卷：15
• 期：7
• 页码：2715-2735
• 全文大小：387 K

文摘

A series of (4-substituted prolyl)prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Among those tested, the 4β-[4-(hydroxyphenyl)prolyl]prolinenitriles showed a potent inhibitory activity with a long duration of action. Metabolic formation of the corresponding phenol glucuronates was found to contribute to their long duration of action. The activity profiles of the synthesized compounds are reported and structure–activity relationships are also presented.