Design, syntheses, and structure–activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H

详细信息    查看全文

• 作者：Yoshio Ogino ; Norikazu Ohtake ; Yoshikazu Nagae ; Kenji Matsuda ; Minoru Moriya ; Takuya Suga ; Makoto Ishikawa ; Maki Kanesaka ; Yuko Mitobe ; Junko Ito ; Tetsuya Kanno ; Akane Ishihara ; Hisashi Iwaasa ; Tomoyu
• 关键词：Neuropeptide Y ; Y5 receptor ; Antagonist ; Anti-obesity ; Benzimidazole
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：15 September 2008
• 年：2008
• 卷：18
• 期：18
• 页码：5010-5014
• 全文大小：193 K

文摘

Design, syntheses, and structure–activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By optimizing substituents on the benzimidazole core part of the lead compound 5a, we were able to develop a potent, orally available, and brain-penetrable Y5 selective antagonist (5k).