3-propionyl-3,8-diazabicyclo<3.2.1>octane | 67571-93-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 3-propionyl-3,8-diazabicyclo<3.2.1>octane
• 英文别名: 3-propionyl-3,8-diaza-bicyclo[3.2.1]octane；1-(3,8-Diazabicyclo[3.2.1]octan-3-yl)propan-1-one
• CAS: 67571-93-1
• 化学式: C₉H₁₆N₂O
• 分子量: 168.239
• InChiKey: ZKOHVSCGMKYLTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-propionyl-3,8-diazabicyclo<3.2.1>octane 在 sodium hydroxide 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 8-(6-chloro-3-pyridazinyl)-3,8-diazabicyclo[3.2.1]octane
  参考文献：
  名称：

  单取代和二取代的3,8-二氮杂双环[3.2.1]辛烷衍生物作为与依巴替丁结构相关的止痛药：合成，活性和建模。

  摘要：

  合成了一系列3,8-二氮杂双环[3.2.1]辛烷，它们在3位（化合物1）或8位（化合物2）被氯代杂芳基环取代，作为强效天然止痛剂Epibatidine的潜在类似物。当在热板试验中测试时，大多数化合物显示出显着效果，最有趣的是3-（6-氯-3-吡啶并嗪基）-3,8-二氮杂双环[3.2.1]辛烷（1a）。在1 mg / kg的皮下剂量下，1a导致疼痛阈值显着增加，其作用持续约45分钟。1a在小鼠腹部收缩试验中以5 mg / kg的剂量也表现出良好的保护作用，而在20 mg / kg的剂量下，它完全阻止了动物的收缩。纳洛酮（1 mg / kg腹膜内）的给药不会拮抗其抗伤害感受，而美加明（2 mg / kg腹膜内）则能拮抗其伤害感受，因此暗示烟碱系统参与其作用。结合研究证实了对α4 beta 2 nAChR亚型的高度亲和力（Ki = 4.1 +/- 0.21 nM）。对三种不同细胞系的nAChR功

  DOI：

  10.1021/jm970427p
• 作为产物：
  描述：

  8-propionil-3,8-diazabiciclo<3,2,1>ottano 反应 3.0h， 生成 3-propionyl-3,8-diazabicyclo<3.2.1>octane
  参考文献：
  名称：

  Synthesis and μ-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives

  摘要：

  A new series of analogues (1c-j; 2c-i) of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (1a,b; 2a,b) was synthesized and tested for their affinity towards mu-opioid receptors. Modifications were introduced either at the cinnamyl or the acyl side chains. The majority of the new compounds, with the exception of 1c,j and 2c, showed K-i values better or comparable with those of the models. (C) 1998 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(98)00065-2

文献信息

• Benzocondensed derivatives as rigid analogues of the μ-opioid agonist 3(8)-cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3.2.1]octanes: synthesis, modeling, and affinity
  作者：G Cignarella、D Barlocco、P Vianello、S Villa、G.A Pinna、P Fadda、W Fratta、L Toma、S Gessi

  DOI：10.1016/s0014-827x(98)00084-6

  日期：1998.11

  A new series of rigid analogues (1a-g, 2a-g) of the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane (I) and its reverted isomer 3-propionyl-8-cinnamyl (II) were synthesized, in which the cinnamyl substituent is incorporated in benzocondensed bicyclic systems. Binding assays for the affinity towards mu receptors indicated that, while in the reverted series 2 the beta-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g) favorably compared with II, all compounds 1 displayed a mu-affinity lower than that of the parent I. Modeling studies suggest that the flexibility of the cinnamyl side chain plays an important role for activity. (C) 1998 Elsevier Science S.A. All rights reserved.
• OCCELLI E.; FONTANELLA L.; DIENA A., FARMACO. ED. SCI., 1978, 33, NO 6, 401-420
  作者：OCCELLI E.、 FONTANELLA L.、 DIENA A.

  DOI：——

  日期：——
• Mono- and Disubstituted-3,8-diazabicyclo[3.2.1]octane Derivatives as Analgesics Structurally Related to Epibatidine:  Synthesis, Activity, and Modeling
  作者：Daniela Barlocco、Giorgio Cignarella、Donatella Tondi、Paola Vianello、Stefania Villa、Alessandro Bartolini、Carla Ghelardini、Nicoletta Galeotti、David J. Anderson、Theresa A. Kuntzweiler、Diego Colombo、Lucio Toma

  DOI：10.1021/jm970427p

  日期：1998.2.1

  A series of 3,8-diazabicyclo[3.2.1]octanes substituted either at the 3 position (compounds 1) or at the 8 position (compounds 2) by a chlorinated heteroaryl ring were synthesized, as potential analogues of the potent natural analgesic epibatidine. When tested in the hot plate assay, the majority of the compounds showed significant effects, the most interesting being the 3-(6-chloro-3-pyridazinyl)-3

  合成了一系列3,8-二氮杂双环[3.2.1]辛烷，它们在3位（化合物1）或8位（化合物2）被氯代杂芳基环取代，作为强效天然止痛剂Epibatidine的潜在类似物。当在热板试验中测试时，大多数化合物显示出显着效果，最有趣的是3-（6-氯-3-吡啶并嗪基）-3,8-二氮杂双环[3.2.1]辛烷（1a）。在1 mg / kg的皮下剂量下，1a导致疼痛阈值显着增加，其作用持续约45分钟。1a在小鼠腹部收缩试验中以5 mg / kg的剂量也表现出良好的保护作用，而在20 mg / kg的剂量下，它完全阻止了动物的收缩。纳洛酮（1 mg / kg腹膜内）的给药不会拮抗其抗伤害感受，而美加明（2 mg / kg腹膜内）则能拮抗其伤害感受，因此暗示烟碱系统参与其作用。结合研究证实了对α4 beta 2 nAChR亚型的高度亲和力（Ki = 4.1 +/- 0.21 nM）。对三种不同细胞系的nAChR功
• Synthesis and μ-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives
  作者：D. Barlocco、G. Cignarella、P. Vianello、S. Villa、G.A. Pinna、P. Fadda、W. Fratta

  DOI：10.1016/s0014-827x(98)00065-2

  日期：1998.8

  A new series of analogues (1c-j; 2c-i) of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (1a,b; 2a,b) was synthesized and tested for their affinity towards mu-opioid receptors. Modifications were introduced either at the cinnamyl or the acyl side chains. The majority of the new compounds, with the exception of 1c,j and 2c, showed K-i values better or comparable with those of the models. (C) 1998 Elsevier Science S.A. All rights reserved.