N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophen-3-carboximidamide | 925216-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophen-3-carboximidamide
• 英文别名: N-[1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl]thiophene-3-carboximidamide；N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophene-3-carboximidamide；N'-[1-[2-(diethylamino)ethyl]-2-[(4-ethoxyphenyl)methyl]benzimidazol-5-yl]thiophene-3-carboximidamide
• CAS: 925216-65-5
• 化学式: C₂₇H₃₃N₅OS
• 分子量: 475.658
• InChiKey: ZCKDTLAYEJZFOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophen-3-carboximidamide 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 0.17h， 生成 N'-[1-[2-(diethylamino)ethyl]-2-[(4-ethoxyphenyl)methyl]benzimidazol-5-yl]thiophene-3-carboximidamide;hydrochloride
  参考文献：
  名称：

  NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

  摘要：

  A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the mu-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the mu-opioid GPCR was predicated on the modulatory role of nitric oxide on mu-opioid receptor function. Structure activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 mu M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent mu-opioid binding affinity, K-i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 mu M). This work represents a novel approach in the development of new analgesics for the treatment of pain.

  DOI：

  10.1021/ml200268w
• 作为产物：
  描述：

  N(1)-(2-(二乙基氨基)乙基)-4-硝基苯-1,2-二胺 在 palladium 10% on activated carbon 、 氢气 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三氯化磷 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 92.0h， 生成 N-(1-(2-(diethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophen-3-carboximidamide
  参考文献：
  名称：

  NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

  摘要：

  A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the mu-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the mu-opioid GPCR was predicated on the modulatory role of nitric oxide on mu-opioid receptor function. Structure activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 mu M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent mu-opioid binding affinity, K-i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 mu M). This work represents a novel approach in the development of new analgesics for the treatment of pain.

  DOI：

  10.1021/ml200268w

文献信息

• Substituted benzimidazole compounds with dual NOS inhibitory activity and mu opioid agonist activity
  申请人：Renton Paul

  公开号：US20080214613A1

  公开（公告）日：2008-09-04

  The present invention relates to benzimidazole compounds having dual nitric oxide synthase (NOS) inhibitory activity and agonist activity at the mu-opioid receptor, to pharmaceutical and diagnostic compositions containing them, and to their medical use, particularly as compounds for the treatment or prevention of chronic pain, acute pain, migraine, and neuropathic pain.

  本发明涉及具有双重一氧化氮合酶（NOS）抑制活性和μ-阿片受体激动活性的苯并咪唑化合物，以及包含它们的药物和诊断组合物，以及它们的医学用途，特别是作为治疗或预防慢性疼痛、急性疼痛、偏头痛和神经病性疼痛的化合物。
• SUBSTITUTED BENZIMIDAZOLE COMPOUNDS WITH DUAL NOS INHIBITORY ACTIVITY AND MUOPIOID AGONIST ACTIVITY
  申请人：Neuraxon Inc.

  公开号：EP1888568A2

  公开（公告）日：2008-02-20
• EP1888568A4
  申请人：——

  公开号：EP1888568A4

  公开（公告）日：2009-08-12
• US7919510B2
  申请人：——

  公开号：US7919510B2

  公开（公告）日：2011-04-05
• [EN] SUBSTITUTED BENZIMIDAZOLE COMPOUNDS WITH DUAL NOS INHIBITORY ACTIVITY AND MUOPIOID AGONIST ACTIVITY<br/>[FR] COMPOSES DE BENZIMIDAZOLE SUBSTITUES A ACTION A LA FOIS INHIBITRICE DE NOS ET AGONISTE OPIOIDE MU
  申请人：NEURAXON INC

  公开号：WO2007017764A2

  公开（公告）日：2007-02-15

  (EN) The present invention relates to benzimidazole compounds having dual nitric oxide synthase (NOS) inhibitory activity and agonist activity at the mu- opioid receptor, to pharmaceutical and diagnostic compositions containing them, and to their medical use, particularly as compounds for the treatment or prevention of chronic pain, acute pain, migraine, and neuropathic pain.(FR) La présente invention porte sur des composés de benzimidazole présentant à la fois une action inhibitrice de la synthase d'oxyde nitrique (NOS) et une action agoniste au niveau du récepteur opioïde mu, sur des compositions pharmaceutiques et diagnostiques les contenant et sur leur utilisation médicale, en particulier comme composés pour le traitement ou la prévention de la douleur chronique, de la douleur aiguë, de la migraine et de la douleur neuropathique.