7-oxa-3-azabicyclo[4.1.0]heptan-3-yl(phenyl)methanone | 71785-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 7-oxa-3-azabicyclo[4.1.0]heptan-3-yl(phenyl)methanone
• 英文别名: 1-benzoyl-3,4-epoxypiperidine；3,4-Epoxy-N-benzoyl piperidine
• CAS: 71785-92-7
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: KOWDPLMDDQJQPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-oxa-3-azabicyclo[4.1.0]heptan-3-yl(phenyl)methanone 在 氢氧化钾 、 4 A molecular sieve 、 双(对硝基苯基)磷酸酯 、 sodium cyanoborohydride 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 67.0h， 生成 1-methylpiperidine-trans-3,4-diol acetonide
  参考文献：
  名称：

  Synthesis and selective activity of cholinergic agents with rigid skeletons. III.

  摘要：

  顺式和反式-哌啶-3, 4-二醇乙酰酮的二甲基季铵盐（9和15）是由易于获得的中间体1-苯甲酰基和1-乙氧基碳酰基的1, 2, 5, 6-四氢吡啶衍生物（4a和4b）制备而成。对9的活性进行了研究，并表明刚性骨架的存在显著降低了与部分打开骨架相比的胆碱仿效效应。讨论了9与已知的强效毒蕈碱剂之间的关系。

  DOI：

  10.1248/cpb.29.3026
• 作为产物：
  描述：

  1,2,3,6-四氢吡啶 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 7-oxa-3-azabicyclo[4.1.0]heptan-3-yl(phenyl)methanone
  参考文献：
  名称：

  Synthesis and in Vitro Biological Evaluation of Carbonyl Group-Containing Analogues for σ₁ Receptors

  摘要：

  To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1)(K-i = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K-i > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K-i = 44.2 nM). The compound [1'-(4-fluorobenzy1)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanone (14a) displayed very high affinity and selectivity for sigma(1) receptor (K-i = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.

  DOI：

  10.1021/jm200203f

文献信息

• Compounds comprising 4-benzoylpiperidine as a Sigma-1-selective ligand
  申请人：Tu Zhude

  公开号：US20110311447A1

  公开（公告）日：2011-12-22

  Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ 1 receptors. Some compounds are also highly selective for σ 1 receptor compared to σ 2 receptor. Compounds can comprise radioisotopes, including 18 F or 11 C. Radiolabeled compounds can be used as probes for imaging distribution of σ 1 receptor in a subject such as a human using positron emission tomography (PET) scanning.

  双哌啶基化合物及其盐被披露。这些化合物包括对σ1受体具有高亲和力的配体。一些化合物相对于σ2受体也具有高选择性。化合物可以包含放射性同位素，包括18F或11C。放射标记的化合物可用作探针，用于通过正电子发射断层扫描（PET扫描）在受试者（如人类）中成像σ1受体的分布。
• Halogenated naphthyl methoxy piperidines for mapping serotonin
  申请人：Emory University

  公开号：US05919797A1

  公开（公告）日：1999-07-06

  Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

  揭示了对血清素转运体具有强亲和力的卤代萘基甲氧基哌啶类化合物。这些化合物可以通过后期合成与正电子发射和/或伽马发射的卤素同位素标记，从而最大限度地延长标记的可用寿命。标记的化合物可用于通过正电子发射断层扫描和/或单光子发射计算机断层扫描定位血清素转运体位点。
• Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand
  申请人：Tu Zhude

  公开号：US08658131B2

  公开（公告）日：2014-02-25

  Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ1 receptors. Some compounds are also highly selective for σ1 receptor compared to σ2 receptor. Compounds can comprise radioisotopes, including 18F or 11C. Radiolabeled compounds can be used as probes for imaging distribution of σ1 receptor in a subject such as a human using positron emission tomography (PET) scanning.

  本文披露了Bipiperidinyl化合物及其盐。这些化合物包括σ1受体的高亲和力配体。一些化合物与σ2受体相比高度选择性地作用于σ1受体。化合物可以包含放射性同位素，包括18F或11C。放射性标记的化合物可用作探针，通过正电子发射断层扫描（PET扫描）成像研究主体（如人体）中σ1受体的分布。
• Nonsymmetrical bipiperidyls as inhibitors of vesicular acetylcholine storage
  作者：S. M. N. Efange、A. Khare、S. M. Parsons、R. Bau、T. Metzenthin

  DOI：10.1021/jm00060a005

  日期：1993.4

  Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-aza-vesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less potent than vesamicol. N-Benzoylation of 5 (to yield 9a) increased the potency 3-fold. In contrast, 10a, a compound derived from N-benzoylation of 6, was 50 times more potent than the latter and almost equipotent with vesamicol, thereby suggesting a preference for the 4-azavesamicol series. Although (-)-vesamicol is more potent than its dextrorotary isomer, (+)-10a was found to be 3 times more potent than (-)-10a, suggesting a reversal of the sign of rotation in the azavesamicol series. Reduction of 9a and 10a (to yield the corresponding N-benzyl derivatives 11a and 12a) increased potency 20- and 2-fold, respectively, indicating a preference for a basic nitrogen. The reaction of 5 or 6 with substituted benzyl halides yielded several potent inhibitors of vesicular acetylcholine transport, including N-(p-fluorobenzyl)trozamicol, 12d, which is twice as potent as vesamicol. Thus the introduction of a nitrogen atom into the cyclohexane ring of vesamicol provides opportunities for developing a new class of anticholinergic agents.
• SAAVEDRA J. E., J. ORG. CHEM., 1979, 44, NO 25, 4516-4518
  作者：SAAVEDRA J. E.

  DOI：——

  日期：——