(E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime | 1224432-92-1

• 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: (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime
• 英文别名: trans-3-[(pyridine-2-yl)ethynyl]cyclohex-2-enone oxime；(E)-3-(Pyridin-2-ylethynyl)cyclohex-2-en-1-one oxime；(NE)-N-[3-(2-pyridin-2-ylethynyl)cyclohex-2-en-1-ylidene]hydroxylamine
• CAS: 1224432-92-1
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: ZWBSNTSHJZOYAE-FYWRMAATSA-N

物化性质

• 沸点：
  391.0±42.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-二氟吡啶 、 (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 以51%的产率得到(E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-6-fluoropyridin-2-yl oxime
  参考文献：
  名称：

  Structure−Activity Relationships of Fluorinated (E)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyloxime (ABP688) Derivatives and the Discovery of a High Affinity Analogue as a Potential Candidate for Imaging Metabotropic Glutamate Recepors Subtype 5 (mGluR5) with Positron Emission Tomography (PET)

  摘要：

  The metabotropic glutamate receptor subtype 5 (mGluR5) is recognized to be involved in numerous brain disorders. In an effort to obtain a fluorine-18 labeled analogue of the mGluR5 PET tracer [C-11]ABP688, 13 novel ligands based on the core structure of ABP688 were synthesized. Molecules in which the methyl group at the oxime functionality of ABP688 was replaced by fluorobenzonitriles, fluoropyridines, and fluorinated oxygen containing alkyl side chains were investigated. Substituents at the oxime functionality are well tolerated and resulted in five candidates with K-i values below 10 nM. The most promising candidate, (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone-O-2-(2-fluoroethoxy)-ethyloxime (38, K-i = 3.8 nM), was radiolabeled with fluorine-18. Scatchard analysis of [F-18]38 which modeled best for two sites pointed to high binding affinity (K-D1 = 0.61 +/- 0.19 nM and K-D2 = 13.73 +/- 4.69 nM) too. These data strongly suggest the further evaluation of [F-18]38 as a candidate for imaging the mGluR5.

  DOI：

  10.1021/jm901850k
• 作为产物：
  描述：

  2-溴吡啶 、 (E)-3-ethynylcyclohex-2-enoneoxime 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到(E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime
  参考文献：
  名称：

  Structure−Activity Relationships of Fluorinated (E)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyloxime (ABP688) Derivatives and the Discovery of a High Affinity Analogue as a Potential Candidate for Imaging Metabotropic Glutamate Recepors Subtype 5 (mGluR5) with Positron Emission Tomography (PET)

  摘要：

  The metabotropic glutamate receptor subtype 5 (mGluR5) is recognized to be involved in numerous brain disorders. In an effort to obtain a fluorine-18 labeled analogue of the mGluR5 PET tracer [C-11]ABP688, 13 novel ligands based on the core structure of ABP688 were synthesized. Molecules in which the methyl group at the oxime functionality of ABP688 was replaced by fluorobenzonitriles, fluoropyridines, and fluorinated oxygen containing alkyl side chains were investigated. Substituents at the oxime functionality are well tolerated and resulted in five candidates with K-i values below 10 nM. The most promising candidate, (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone-O-2-(2-fluoroethoxy)-ethyloxime (38, K-i = 3.8 nM), was radiolabeled with fluorine-18. Scatchard analysis of [F-18]38 which modeled best for two sites pointed to high binding affinity (K-D1 = 0.61 +/- 0.19 nM and K-D2 = 13.73 +/- 4.69 nM) too. These data strongly suggest the further evaluation of [F-18]38 as a candidate for imaging the mGluR5.

  DOI：

  10.1021/jm901850k

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSES HETEROCYCLIQUES ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：MERCK & CO INC

  公开号：WO2001016121A1

  公开（公告）日：2001-03-08

  In accordance with the present invention, there are provided novel class of heterocyclic compounds and methods of use thereof. Compounds of the invention contain a substituted, unsaturated five, six or seven membered heterocyclic ring that includes at least one nitrogen atom and at least one carbon atom. At a ring position adjacent to a ring nitrogen atom, the heterocyclic ring has at least one substituent which includes a moiety, linked to the heterocyclic ring via an alkylene moiety, an alkynylene moiety or an azo group. Invention compounds are capable of a wide variety of uses including modulating physiological processes by functioning as agonists and antagonists of receptors in the nervous system, as insecticides, and as fungicides. The invention further provides methods of modulating the activity of excitatory amino acid receptors using a specifically defined class of heterocyclic compounds including the novel compounds referred to above. In one embodiment, there are provided methods of modulating metabotropic glutamate receptors. The present invention also discloses methods of treating disease using heterocyclic compounds. The invention further discloses methods of preventing disease conditions related to diseases of the pulmonary system, diseases of the nervous system, diseases of the cardiovascular system, diseases of the gastrointestinal system, diseases of the endocrine system, diseases of the exocrine system, diseases of the skin, cancer and diseases of the ophthalmic system. The invention also discloses pharmaceutically acceptable salt forms of the above-described heterocyclic compounds.

  根据本发明，提供了一类新型的杂环化合物及其使用方法。该发明的化合物包含一个取代的、不饱和的五、六或七元杂环环，其中至少包含一个氮原子和至少一个碳原子。在靠近环氮原子的环位置上，杂环环有至少一个取代基，包括一个官能团，通过烷基官能团、炔基官能团或偶氮基团连接到杂环环上。发明的化合物能够广泛应用，包括通过作为神经系统受体的激动剂和拮抗剂来调节生理过程，作为杀虫剂和杀菌剂。本发明还提供了使用特定定义的杂环化合物类来调节兴奋性氨基酸受体活性的方法，包括上述新型化合物。在一种实施例中，提供了调节代谢性谷氨酸受体的方法。本发明还揭示了使用杂环化合物治疗疾病的方法。本发明还揭示了预防与肺系统疾病、神经系统疾病、心血管系统疾病、胃肠系统疾病、内分泌系统疾病、外分泌系统疾病、皮肤疾病、癌症和眼科系统疾病相关的疾病状态的方法。本发明还揭示了上述杂环化合物的药物可接受的盐形式。
• Synthesis and In Vitro Evaluation of E- and Z-Geometrical Isomers of PSS232 as Potential Metabotropic Glutamate Receptors Subtype 5 (mGlu5) Binders
  作者：Selena Milicevic Sephton、Simon Ametamey、Linjing Mu、Martina Dragic、Stefanie Krämer、Roger Schibli

  DOI：10.1055/s-0033-1338843

  日期：——

  Based on the core structure of [C-11]-ABP688, our group developed a novel fluorine-18 labeled PET radiotracer, (E)-[F-18]-PSS232, with significantly improved in vivo properties compared to the earlier fluorine-18 derivative [F-18]-FDEGPECO. The synthetic approach used to obtain PSS232 and the radiolabeling precursor mesylate is disclosed as well as the evaluation of the two geometrical isomers of PSS232. In vitro displacement assays showed higher binding affinity of the E-geometrical isomer (1 nM vs 15 nM, for Z-isomer), which was, for this reason, selected for radiolabeling. One-step radiolabeling conditions (K-222/F-18(-), DMSO, 95 degrees C, 10 min) to synthesize (E)-[F-18]- PSS232 from the mesylate via nucleophilic substitution are described. At ambient temperature, (E)-[F-18]-PSS232, with log D-7.4 value of 2.0, was chemically stable over six hours in the presence of sodium ascorbate as a radical scavenger.
• HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Merck & Co., Inc.

  公开号：EP1214303A1

  公开（公告）日：2002-06-19
• Structure−Activity Relationships of Fluorinated (<i>E</i>)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-<i>O</i>-methyloxime (ABP688) Derivatives and the Discovery of a High Affinity Analogue as a Potential Candidate for Imaging Metabotropic Glutamate Recepors Subtype 5 (mGluR5) with Positron Emission Tomography (PET)
  作者：Cindy A. Baumann、Linjing Mu、Sinja Johannsen、Michael Honer、Pius A. Schubiger、Simon M. Ametamey

  DOI：10.1021/jm901850k

  日期：2010.5.27

  The metabotropic glutamate receptor subtype 5 (mGluR5) is recognized to be involved in numerous brain disorders. In an effort to obtain a fluorine-18 labeled analogue of the mGluR5 PET tracer [C-11]ABP688, 13 novel ligands based on the core structure of ABP688 were synthesized. Molecules in which the methyl group at the oxime functionality of ABP688 was replaced by fluorobenzonitriles, fluoropyridines, and fluorinated oxygen containing alkyl side chains were investigated. Substituents at the oxime functionality are well tolerated and resulted in five candidates with K-i values below 10 nM. The most promising candidate, (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone-O-2-(2-fluoroethoxy)-ethyloxime (38, K-i = 3.8 nM), was radiolabeled with fluorine-18. Scatchard analysis of [F-18]38 which modeled best for two sites pointed to high binding affinity (K-D1 = 0.61 +/- 0.19 nM and K-D2 = 13.73 +/- 4.69 nM) too. These data strongly suggest the further evaluation of [F-18]38 as a candidate for imaging the mGluR5.