1-naphthalen-2-ylmethylpiperidin-4-one ethylene ketal | 898222-58-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 1-naphthalen-2-ylmethylpiperidin-4-one ethylene ketal
• 英文别名: 8-(Naphthalen-2-ylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane
• CAS: 898222-58-7
• 化学式: C₁₈H₂₁NO₂
• 分子量: 283.37
• InChiKey: LAHZTTNMGSRQEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-naphthalen-2-ylmethylpiperidin-4-one ethylene ketal 在 盐酸 、 氨 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 26.0h， 生成 4-(aminomethyl)-1-(naphthalen-2-ylmethyl)-N-phenylpiperidin-4-amine
  参考文献：
  名称：

  Nonpeptide Small Molecule Agonist and Antagonist Original Leads for Neuropeptide FF1 and FF2 Receptors

  摘要：

  Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, K-i = 487 +/- 117 nM), a NPFF1 antagonist (46, K-i = 81 +/- 17 nM), and a NPFF2 partial antagonist (53a, K-i = 30 +/- 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 degrees C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.

  DOI：

  10.1021/jm500989n
• 作为产物：
  描述：

  4-哌啶酮缩乙二醇 、 2-萘甲醛 在 哌啶酮 、 sodium tetrahydroborate 、 N,N-diisopropyl-4H-benzo[d][1,3,2]dioxaborinin-2-amine 作用下， 以 1,2-二氯乙烷 为溶剂， 以93%的产率得到1-naphthalen-2-ylmethylpiperidin-4-one ethylene ketal
  参考文献：
  名称：

  Reductive Amination of Aldehydes Using Aminoboranes as Iminium Ion Generators

  摘要：

  2-二烷基氨基-4H-1,3,2-苯并二氧硼烷和基于水杨醇的氨基硼烷在与NaBH4的还原胺化反应中，作为高效且温和的亚胺离子生成剂。使用二异丙基氨基衍生物，二级和初级胺以及氨可以在无质子有机溶剂中参与还原胺化，而无需使用酸性促进剂。

  DOI：

  10.1055/s-2006-939070

文献信息

• Discovery and SAR of a Novel Selective and Orally Bioavailable Nonpeptide Classical Competitive Inhibitor Class of Protein-Tyrosine Phosphatase 1B
  作者：Henrik Sune Andersen、Ole H. Olsen、Lars F. Iversen、Anette L. P. Sørensen、Steen B. Mortensen、Michael S. Christensen、Sven Branner、Thomas K. Hansen、Jesper F. Lau、Lone Jeppesen、Edmond J. Moran、Jing Su、Farid Bakir、Luke Judge、Manou Shahbaz、Tassie Collins、Todd Vo、Michael J. Newman、William C. Ripka、Niels Peter H. Møller

  DOI：10.1021/jm0209026

  日期：2002.9.1

  Reversible phosphorylation and dephosphorylation of key proteins on tyrosine residues are important parts of intracellular signaling triggered by hormones and other agents. Recent knock-out studies in mice have identified PTP1B as a potential target for the treatment of diabetes and obesity. As a consequence, a number of academic and industrial groups are aggressively pursuing the development of selective PTP1B inhibitors. In addition, other protein-tyrosine phosphatases (PTPs) appear to be critically involved in major diseases such as cancer and autoimmunity. Given the diversity of PTPs and their potential as drug targets in different diseases, we have taken a broad approach to develop active site-directed selective inhibitors of specific members of this family of enzymes. Using a high throughput screening, we have previously identified 2-(oxalylamino)benzoic acid 3a as a relatively weak but classical competitive inhibitor of several PTPs.(4) On the basis of our early studies, indicating that 3a might be used as a starting point for the synthesis of selective PTP inhibitors, we now present our efforts in expansion of this concept and provide here a number of new chemical scaffolds for the development of inhibitors of different members of the PTP family. Although the core structure of these inhibitors is charged, good oral bioavailability has been observed in rat for some compounds. Furthermore, we have observed enhancement of 2-deoxy-glucose accumulation in C2C12 cells with prodrug analogues.