N-(4-bromo-2-(2,2-dimethoxyethyl)phenyl)-quinuclidin-3-amine | 954387-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: N-(4-bromo-2-(2,2-dimethoxyethyl)phenyl)-quinuclidin-3-amine
• 英文别名: N-[4-bromo-2-(2,2-dimethoxyethyl)phenyl]-1-azabicyclo[2.2.2]octan-3-amine
• CAS: 954387-00-9
• 化学式: C₁₇H₂₅BrN₂O₂
• 分子量: 369.302
• InChiKey: DMVDFVGIVHSSLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  33.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-bromo-2-(2,2-dimethoxyethyl)phenyl)-quinuclidin-3-amine 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 生成 N-(1-(Quinuclidin-3-yl)-1H-indol-5-yl)thiophene-2-carboximidamide
  参考文献：
  名称：

  1,5-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors

  摘要：

  A series of 1,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase. A variety of flexible and restricted basic amine side chain substitutions was explored at the 1-position of the indole ring, while keeping the amidine group fixed at the 5-position. Compounds having N-(1-(2-(1-methylpyrrolidin-2-yl) ethyl)- (12, (R)-12, (S)-12 and 13) and N-(1-(1-methylazepan-4-yl)-side chains (14, 15, (-)-15 and (+)-15) showed increased inhibitory activity for the human nNOS isoform and selectivity over eNOS and iNOS isoforms. The most potent compound of the series for human nNOS (IC(50) = 0.02 mu M) (S)-12 showed very good selectivity over the eNOS (eNOS/nNOS = 96-fold) and iNOS (iNOS/nNOS = 850-fold) isoforms. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.022
• 作为产物：
  描述：

  4-Bromo-2-(2,2-dimethoxyethyl)-1-nitrobenzene 在 sodium dithionite 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 sodium sulfate 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 生成 N-(4-bromo-2-(2,2-dimethoxyethyl)phenyl)-quinuclidin-3-amine
  参考文献：
  名称：

  1,5-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors

  摘要：

  A series of 1,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase. A variety of flexible and restricted basic amine side chain substitutions was explored at the 1-position of the indole ring, while keeping the amidine group fixed at the 5-position. Compounds having N-(1-(2-(1-methylpyrrolidin-2-yl) ethyl)- (12, (R)-12, (S)-12 and 13) and N-(1-(1-methylazepan-4-yl)-side chains (14, 15, (-)-15 and (+)-15) showed increased inhibitory activity for the human nNOS isoform and selectivity over eNOS and iNOS isoforms. The most potent compound of the series for human nNOS (IC(50) = 0.02 mu M) (S)-12 showed very good selectivity over the eNOS (eNOS/nNOS = 96-fold) and iNOS (iNOS/nNOS = 850-fold) isoforms. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.022

文献信息

• 1,5 And 3,6- substituted indole compounds having NOS inhibitory activity
  申请人：Maddaford Shawn

  公开号：US20070254940A1

  公开（公告）日：2007-11-01

  The present invention features inhibitors of nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing conditions such as, for example, stroke, reperfusion injury, neurodegeneration, head trauma, CABG, migraine headache with and without aura, migraine with allodynia, central post-stroke pain (CPSP), neuropathic pain, or chronic pain.

  本发明涉及一种一氧化氮合酶（NOS）的抑制剂，特别是那些选择性地抑制神经一氧化氮合酶（nNOS）而不是其他NOS同工酶。本发明的NOS抑制剂，单独或与其他药用活性剂联合使用，可用于治疗或预防诸如中风、再灌注损伤、神经退行性疾病、头部创伤、冠状动脉搭桥手术（CABG）、有或无先兆的偏头痛、伴有触痛的偏头痛、中枢性中风后疼痛（CPSP）、神经病性疼痛或慢性疼痛等病症。
• 1,5 and 3,6-substituted indole compounds having NOS inhibitory activity
  申请人：NeurAxon, Inc.

  公开号：US07989447B2

  公开（公告）日：2011-08-02

  The present invention features inhibitors of nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing conditions such as, for example, stroke, reperfusion injury, neurodegeneration, head trauma, CABG, migraine headache with and without aura, migraine with allodynia, central post-stroke pain (CPSP), neuropathic pain, or chronic pain.

  本发明涉及一种一氧化氮合酶（NOS）抑制剂，特别是那些能够选择性地抑制神经型一氧化氮合酶（nNOS）而不影响其他NOS同工酶。本发明的NOS抑制剂可以单独或与其他药物活性剂联合使用，用于治疗或预防中风、再灌注损伤、神经退行性疾病、头部创伤、冠状动脉搭桥术（CABG）、带和不带先兆的偏头痛、带有痛觉过敏的偏头痛、中枢后中风痛（CPSP）、神经性疼痛或慢性疼痛等症状。
• 1,5 AND 3,6- SUBSTITUTED INDOLE COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
  申请人：Neuraxon Inc.

  公开号：EP2010527B1

  公开（公告）日：2013-08-14
• US7989447B2
  申请人：——

  公开号：US7989447B2

  公开（公告）日：2011-08-02
• [EN] 1,5 AND 3,6- SUBSTITUTED INDOLE COMPOUNDS HAVING NOS INHIBITORY ACTIVITY<br/>[FR] INDOLES 1,5- ET 3,6-SUBSTITUÉS À ACTIVITÉ INHIBITRICE VIS-À-VIS DE NOS
  申请人：NEURAXON INC

  公开号：WO2007118314A1

  公开（公告）日：2007-10-25

  [EN] The present invention features inhibitors of nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing conditions such as, for example, stroke, reperfusion injury, neurodegeneration, head trauma, CABG, migraine headache with and without aura, migraine with allodynia, central post-stroke pain (CPSP), neuropathic pain, or chronic pain.
  [FR] La présente invention concerne des inhibiteurs de l'oxyde nitrique synthétase (NOS), en particulier ceux qui inhibent de façon sélective l'oxyde nitrique synthétase neuronale (nNOS) préférentiellement aux autres isoformes de NOS. Les inhibiteurs de NOS selon l'invention, seuls ou combinés à d'autres principes actifs pharmaceutiques, peuvent être employés dans le traitement prophylactique ou thérapeutique d'états pathologiques tels que, par exemple, les accidents cérébrovasculaires, les lésions de reperfusion, la neurodégénérescence, les traumatismes crâniens, les pontages coronariens, les migraines avec et sans aura, les migraines avec allodynie, les douleurs centrales après accidents cérébrovasculaires, les douleurs névropathiques ou les douleurs chroniques.