Pyrrolo[1,2-b]pyridazines, pyrrolo[2,1-f]triazin-4(3H)-ones, and related compounds as novel corticotropin-releasing factor 1 (CRF₁) receptor antagonists

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• 作者：Tetsuji Saito ; ^{te.saitou@ono.co.jp} ; Tetsuo Obitsu ; Hiroshi Kohno ; Isamu Sugimoto ; Takeshi Matsushita ; Taihei Nishiyama ; Tomoko Hirota ; Hiroyuki Takeda ; Naoya Matsumura ; Sonoko Ueno ; Akihiro Kishi ; Yoshifumi Kagamiishi ; Hisao Nakai ; Yoshikazu Takaoka
• 关键词：Corticotropin-releasing factor 1 receptor ; Antagonist
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：15 January, 2012
• 年：2012
• 卷：20
• 期：2
• 页码：1122-1138
• 全文大小：838 K

文摘

To identify structurally novel corticotropin-releasing factor 1 (CRF₁) receptor antagonists, a series of bicyclic core analogs pyrrolo[1,2-b]pyridazines and pyrrolo[2,1-f]triazin-4(3H)-ones, which were designed based on a monocyclic core antagonist, was synthesized and evaluated. Among the compounds tested, 2-difluoromethoxy-4-methylpyridin-5-yl analog 27 was found to show efficacy in a dose-dependent manner in an elevated plus maze test in rats. The discovery process and structure-activity relationship is presented.