trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile | 1075736-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile
• CAS: 1075736-35-4
• 化学式: C₁₄H₁₃NO₂
• 分子量: 227.263
• InChiKey: CXXJOLPNEDMUBP-YPFXGUDJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  17.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  50.09
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile 在 硫酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 以96%的产率得到trans-3-oxospiro[isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxylic acid
  参考文献：
  名称：

  新型，强效和选择性反式-2- [3-氧螺环[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及构效关系。

  摘要：

  描述了新型的2- [3-氧杂螺[异苯并呋喃-1（3H），1'-环己基] -4'-基]苯并咪唑NPY Y5受体拮抗剂的合成及其构效关系。通过将取代基并入苯并咪唑核心部分的5位或5位和6位两者中来优化前导化合物2a导致鉴定出5-（5-甲基-1,2,4-恶二唑-2 -基）苯并咪唑（2r：IC（50）= 3.3 nM）和5-（2-甲基四唑-5-基）苯并咪唑（2u：IC（50）= 5.9 nM），两者都是有效的，选择性的和口服的可生物利用的Y5受体拮抗剂。

  DOI：

  10.1016/j.bmcl.2008.08.021
• 作为产物：
  描述：

  cis-4'-hydroxy-3H-spiro[2-benzofuran-1,1'-cyclohexan]-3-one 、 氰化四乙基铵 以 N,N-二甲基甲酰胺 为溶剂， 生成 trans-3-oxo-3H-spiro[2-benzofuran-1,1'-cyclohexane]-4'-carbonitrile
  参考文献：
  名称：

  Identification of positron emission tomography ligands for NPY Y5 receptors in the brain

  摘要：

  A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized and profiled for NPY Y5 binding affinity, brain and CSF penetrability in rats, and susceptibility to human and mouse P-glycoprotein transporters in order to develop a PET ligand. Compound 12b exhibited an acceptable profile for a PET ligand, and [C-11]12b was successfully utilized in clinical settings as a Y5 PET ligand. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.103

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.
• Synthesis and evaluation of a spiro-isobenzofuranone class of histamine H3 receptor inverse agonists
  作者：Makoto Jitsuoka、Daisuke Tsukahara、Sayaka Ito、Takeshi Tanaka、Norihiro Takenaga、Shigeru Tokita、Nagaaki Sato

  DOI：10.1016/j.bmcl.2008.07.125

  日期：2008.9

  Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain-penetrable non-imidazole H-3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t-x. Spiro-isobenzofuranone 2x, the most potent among the derivatives, was converted to the corresponding amide 1a, which possessed dramatically improved H3 activity (IC50 = 0.72 nM; more than 20-fold improvement over 2x). Further elaboration led to the identification of 1b, a 5-methoxy derivative with an IC50 of 0.54 nM. Our studies demonstrated that derivatives 1a and 1b to be potent, selective, and brain-penetrable H-3 inverse agonists. (C) 2008 Elsevier Ltd. All rights reserved.