1-(1-(4-methoxybenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

• 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: 1-(1-(4-methoxybenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
• 英文别名: 1-[1-(4-methoxy-benzyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one；1-(4-methoxybenzyl)-4-(2-keto-1-benzoimidazolinyl)-piperidine；3-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-1H-benzimidazol-2-one
• 化学式: C₂₀H₂₃N₃O₂
• 分子量: 337.422
• InChiKey: NIYHACADWRRGMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-甲氧基苯甲醛 、 4-（2-酮酸-1-苯并咪唑）哌啶 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 以77%的产率得到1-(1-(4-methoxybenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
  参考文献：
  名称：

  Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

  摘要：

  While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal beta arrestin-mediated signaling because MOR agonist-treated beta arrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/beta arr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

  DOI：

  10.1021/acs.jmedchem.8b01136

文献信息

• REMEDIES FOR PAIN
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1142587A1

  公开（公告）日：2001-10-10

  The present invention provides a pain control agent, which contains, as an active ingredient, a compound having both µ opioid receptor agonist activity and dopamine D2 receptor antagonist activity. The compound having both of these activities exerts a potent morphine-like analgetic effect and causes no psychological dependence, and even regulates side effects. In particular, a novel compound represented by general formula (I) or a pharmacologically acceptable salt thereof has both µ opioid receptor agonist activity and dopamine D2 receptor antagonist activity, and is useful as pain control agent with regulated side effects.

  本发明提供了一种疼痛控制剂，其包含作为活性成分的化合物具有µ阿片受体激动剂活性和多巴胺D2受体拮抗剂活性。具有这两种活性的化合物具有强效的类鸦片样镇痛作用，并不会导致心理依赖，甚至可以调节副作用。特别是，由通式（I）表示的新化合物或其药理学可接受的盐具有µ阿片受体激动剂活性和多巴胺D2受体拮抗剂活性，并且作为具有调节副作用的疼痛控制剂是有用的。