trans-3-oxo-N-(5-phenylpyridin-2-yl)-3H-spiro[6-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxamide | 1195313-76-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: trans-3-oxo-N-(5-phenylpyridin-2-yl)-3H-spiro[6-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxamide
• CAS: 1195313-76-8
• 化学式: C₂₄H₂₁N₃O₃
• 分子量: 399.449
• InChiKey: DXEFJGPUHYASEM-WVQHILGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  81.18
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  trans-1'-oxospiro[1,3'-cyclohexane(1'H)-furo[3,4-c]pyridine]-4-carboxylic acid 、 2-氨基-5-苯基吡啶 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以54%的产率得到trans-3-oxo-N-(5-phenylpyridin-2-yl)-3H-spiro[6-aza-2-benzofuran-1,1'-cyclohexane]-4'-carboxamide
  参考文献：
  名称：

  Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′-cyclohexane]-4′-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist

  摘要：

  A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized to identify potent NPY Y5 receptor antagonists. Of the compounds, 21j showed high Y5 binding affinity, metabolic stability and brain and cerebrospinal fluid (CSF) penetration, and low susceptibility to P-glycoprotein transporters. Oral administration of 21j significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 1 mg/kg. This compound was selected for proof-of-concept studies in human clinical trials. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.019

文献信息

• Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1′-cyclohexane]-4′-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist
  作者：Yuji Haga、Toshihiro Sakamoto、Takunobu Shibata、Katsumasa Nonoshita、Makoto Ishikawa、Takuya Suga、Hirobumi Takahashi、Toshiyuki Takahashi、Hidekazu Takahashi、Makoto Ando、Takashi Murai、Akira Gomori、Zenjun Oda、Hidefumi Kitazawa、Yuko Mitobe、Maki Kanesaka、Tomoyuki Ohe、Hisashi Iwaasa、Yasuyuki Ishii、Akane Ishihara、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmc.2009.08.019

  日期：2009.10

  A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized to identify potent NPY Y5 receptor antagonists. Of the compounds, 21j showed high Y5 binding affinity, metabolic stability and brain and cerebrospinal fluid (CSF) penetration, and low susceptibility to P-glycoprotein transporters. Oral administration of 21j significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 1 mg/kg. This compound was selected for proof-of-concept studies in human clinical trials. (C) 2009 Elsevier Ltd. All rights reserved.