ethyl 3-{[(trifluoromethyl)sulfonyl]oxy} azabicyclo[3.2.1]oct-2-ene-8-carboxylate | 184368-73-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: ethyl 3-{[(trifluoromethyl)sulfonyl]oxy} azabicyclo[3.2.1]oct-2-ene-8-carboxylate
• 英文别名: Ethyl 3-{[(trifluoromethyl) sulfonyl]oxy}-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate；ethyl 3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate
• CAS: 184368-73-8
• 化学式: C₁₁H₁₄F₃NO₅S
• 分子量: 329.297
• InChiKey: SXIKXEMSYRIPJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 3-{[(trifluoromethyl)sulfonyl]oxy} azabicyclo[3.2.1]oct-2-ene-8-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 碘代三甲硅烷 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  3D QSAR Analyses-Guided Rational Design of Novel Ligands for the (α4)₂(β2)₃ Nicotinic Acetylcholine Receptor

  摘要：

  Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.

  DOI：

  10.1021/jm020859m
• 作为产物：
  描述：

  N-乙氧羰基-4-托品酮 、 三氟甲烷磺基苯胺 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.5h， 生成 ethyl 3-{[(trifluoromethyl)sulfonyl]oxy} azabicyclo[3.2.1]oct-2-ene-8-carboxylate
  参考文献：
  名称：

  [EN] BICYCLIC PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS
  [FR] DERIVES DE PIPERIDINE BICYCLIQUES UTILISES COMME AGONISTES DU RECEPTEUR 4 DE LA MELANOCORTINE

  摘要：

  某些新颖的双环N-酰化哌啶衍生物是人类黑色素皮质素受体的激动剂，特别是人类黑色素皮质素-4受体（MC-4R）的选择性激动剂。因此，它们对于治疗、控制或预防对MC-4R激活敏感的疾病和疾病是有用的，例如肥胖症、糖尿病、性功能障碍，包括勃起功能障碍和女性性功能障碍。

  公开号：

  WO2004087159A1

文献信息

• Bicyclic piperidine derivatives as melanocortin-4 receptor agonists
  申请人：Nargund P. Ravi

  公开号：US20060194780A1

  公开（公告）日：2006-08-31

  Certain novel bicyclic N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

  某些新型双环N-酰化哌啶衍生物是人类黑色素细胞素受体的激动剂，特别是人类黑色素细胞素-4受体(MC-4R)的选择性激动剂。因此，它们可用于治疗、控制或预防对MC-4R激活有响应的疾病和障碍，如肥胖症、糖尿病、性功能障碍，包括勃起功能障碍和女性性功能障碍。
• Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives
  作者：Robert J. Watson、Daniel R. Allen、Helen L. Birch、Gayle A. Chapman、Frances C. Galvin、Louise A. Jopling、Roland L. Knight、Dorica Meier、Kathryn Oliver、Johannes W.G. Meissner、David A. Owen、Elizabeth J. Thomas、Neil Tremayne、Sophie C. Williams

  DOI：10.1016/j.bmcl.2007.10.109

  日期：2008.1

  The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease. (C) 2007 Elsevier Ltd. All rights reserved.
• AZABICYCLO 3.2.1]OCTANE DERIVATIVES
  申请人：ELI LILLY AND COMPANY

  公开号：EP1242419A1

  公开（公告）日：2002-09-25
• EP1610789A1
  申请人：——

  公开号：EP1610789A1

  公开（公告）日：2006-01-04
• EP1610789A4
  申请人：——

  公开号：EP1610789A4

  公开（公告）日：2008-02-27