huperzine A

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: huperzine A
• 英文别名: (1r,9s,13e)-1-Amino-13-ethylidene-11-methyl-6azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-5-one；(1R,9S,13E)-1-amino-13-ethylidene-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-5-one
• 化学式: C₁₅H₁₈N₂O
• 分子量: 242.321
• InChiKey: ZRJBHWIHUMBLCN-DHGMEZGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  huperzine A 在 silver carbonate 、 potassium carbonate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 2.0h， 生成 methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9methanocycloocta[b]pyridin-5-yl)carbamate
  参考文献：
  名称：

  通过串联的分子内氮杂-Prins环化-环丁烷裂解合成（-）-石杉碱甲的新型方法

  摘要：

  乙酰胆碱酯酶抑制剂（-）-石杉碱甲是由（S）-4-羟基环己基-2-烯酮以17个步骤通过涉及两个环丁烷片段化的途径合成的。这些中的第一个采用逆向羟醛裂解生成石杉碱A的α-吡啶酮环，第二个使用串联的新颖分子内氮杂-Prins反应与立体控制的环丁基甲炔基阳离子的断裂产生氨基双环[3.3.1]。天然生物碱的壬烯骨架。

  DOI：

  10.1021/ol400012s
• 作为产物：
  描述：

  methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9methanocycloocta[b]pyridin-5-yl)carbamate 在 碘代三甲硅烷 作用下， 以 氯仿 为溶剂， 反应 6.0h， 以80%的产率得到huperzine A
  参考文献：
  名称：

  通过串联的分子内氮杂-Prins环化-环丁烷裂解合成（-）-石杉碱甲的新型方法

  摘要：

  乙酰胆碱酯酶抑制剂（-）-石杉碱甲是由（S）-4-羟基环己基-2-烯酮以17个步骤通过涉及两个环丁烷片段化的途径合成的。这些中的第一个采用逆向羟醛裂解生成石杉碱A的α-吡啶酮环，第二个使用串联的新颖分子内氮杂-Prins反应与立体控制的环丁基甲炔基阳离子的断裂产生氨基双环[3.3.1]。天然生物碱的壬烯骨架。

  DOI：

  10.1021/ol400012s

文献信息

• COMBINATION OF A NSPACHA (PERIPHERAL ANTICHOLINERGIC AGENT) LIKE SOLIFENACIN AND AN ACHEI (ACETYL CHOLINE ESTERASE INHIBITOR) LIKE DONEPEZIL FOR TREATING DEMENTIA
  申请人：Chase Pharmaceuticals Corporation

  公开号：EP3178477A1

  公开（公告）日：2017-06-14

  There is described a method for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-selective, peripheral anticholinergic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-selective, peripheral anticholinergic agent (nsPAChA) for the preparation of a pharmaceutical composition for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia and pharmaceutical compositions comprising a non-selective peripheral anticholinergic agent of formula II as illustrated in the description and an acetylcholine esterase inhibitor are also described.

  本文描述了一种方法，通过将乙酰胆碱酯酶抑制剂（AChEI）与一种非选择性外周抗胆碱能药物联合使用，降低伴随的不良反应，从而提高乙酰胆碱酯酶抑制剂（AChEI）在阿尔茨海默型痴呆患者中的最大耐受剂量，进而提高其疗效、外周抗胆碱能药物，从而增强对患者中枢神经系统中乙酰胆碱酯酶的抑制作用，并在更大程度上缓解患者的阿尔茨海默型痴呆症状。此外，还描述了使用非选择性外周抗胆碱能剂（nsPAChA）制备药物组合物，以提高最大耐受剂量，从而提高乙酰胆碱酯酶抑制剂（AChEI）在阿尔茨海默型痴呆症患者中的疗效，以及包含描述中所示式 II 的非选择性外周抗胆碱能剂和乙酰胆碱酯酶抑制剂的药物组合物。
• Oxybutynin transdermal therapeutic system combination
  申请人：CHASE PHARMACEUTICALS CORPORATION

  公开号：US10149828B2

  公开（公告）日：2018-12-11

  There is described a pharmaceutical combination comprising oxybutynin or a pharmaceutically acceptable addition salt thereof, in a transdermal therapeutic system, and an acetylcholinesterase inhibitor, useful for safely treating hypocholinergic disorders of the central nervous system such as Alzheimer type dementia. In this combination, the acetylcholinesterase inhibitor (AChEI) is present at a dose that is higher than the maximal recommended dose, per unit form. In particular, the transdermal therapeutic system comprising oxybutynin is in combination with rivastigmine in a transdermal formulation or oral form.

  本文描述了一种药物组合，它包含透皮治疗系统中的奥昔布宁或其药学上可接受的添加盐，以及乙酰胆碱酯酶抑制剂，可用于安全治疗中枢神经系统的低胆碱能疾病，如阿尔茨海默型痴呆症。在这种组合中，乙酰胆碱酯酶抑制剂（AChEI）的单位剂量高于最大推荐剂量。特别是，由奥昔布宁组成的透皮治疗系统与利巴斯的明以透皮制剂或口服形式结合使用。
• Oxybutynin transdermal therapeutic system muscarinic agonist combination
  申请人：CHASE PHARMACEUTICALS CORPORATION

  公开号：US10596139B2

  公开（公告）日：2020-03-24

  Pharmaceutical compositions and combinations containing a muscarinic receptor antagonist, such as oxybutynin in a transdermal therapeutic system, and a muscarinic receptor agonist, optionally with an acetyl cholinesterase inhibitor, and methods of using the same for treatment of hypocholinergic disorders of the central nervous system such as Alzheimer type dementia. The respective pharmaceutical compositions and combinations of the present invention allow for safe administration of high doses of muscarinic receptor agonist, and improved efficacy of the muscarinic receptor agonist for treatment of hypocholinergic disorders of the central nervous system. The pharmaceutical compositions and combinations also allow for a maximum supply of acetylcholine to the central nervous system, when an acetyl cholinesterase inhibitor is used in combination with a muscarinic receptor antagonist and a muscarinic receptor agonist.

  含有毒蕈碱受体拮抗剂（如透皮治疗系统中的奥昔布宁）和毒蕈碱受体激动剂（可选择与乙酰胆碱酯酶抑制剂一起使用）的药物组合物和组合物，以及使用这些药物组合物和组合物治疗中枢神经系统低胆碱能疾病（如阿尔茨海默型痴呆症）的方法。本发明的各种药物组合物和组合物可以安全地施用大剂量毒蕈碱受体激动剂，并提高毒蕈碱受体激动剂治疗中枢神经系统低胆碱能疾病的疗效。当乙酰胆碱酯酶抑制剂与毒蕈碱受体拮抗剂和毒蕈碱受体激动剂联合使用时，本发明的药物组合物和复方制剂还能最大限度地向中枢神经系统提供乙酰胆碱。
• COMBINATION FOR TREATING ALZHEIMER-TYPE DEMENTIA
  申请人：Chase Pharmaceuticals Corporation

  公开号：EP2478099B1

  公开（公告）日：2019-06-05
• USE AND COMPOSITION FOR TREATING DEMENTIA
  申请人：Chase Thomas N.

  公开号：US20130158012A1

  公开（公告）日：2013-06-20

  There is described a method for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-selective, peripheral anticholinergic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-selective, peripheral anticholinergic agent (nsPAChA) for the preparation of a pharmaceutical composition for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia and pharmaceutical compositions comprising a non-selective peripheral anticholinergic agent of formula II as illustrated in the description and an acetylcholine esterase inhibitor are also described.