methoctramine | 104807-40-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methoctramine
• 英文别名: N,N'-bis[6-[[(2-methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine；Methoctramine free base；N,N'-bis[6-[(2-methoxyphenyl)methylamino]hexyl]octane-1,8-diamine
• CAS: 104807-40-1
• 化学式: C₃₆H₆₂N₄O₂
• 分子量: 582.914
• InChiKey: RPMBYDYUVKEZJA-UHFFFAOYSA-N

物化性质

• 沸点：
  681.9±55.0 °C(Predicted)
• 密度：
  0.977±0.06 g/cm3(Predicted)
• 溶解度：
  H2O:≤5 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  42
• 可旋转键数：
  29
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.6
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 methoctramine 在 甲酸 作用下， 以 水 为溶剂， 反应 12.0h， 生成 N,N'-bis[6-{[(2-methoxybenzyl)methyl]amino}hexyl]-N,N'-dimethyl-1,8-octanediamine
  参考文献：
  名称：

  Structure-activity relationships among methoctramine-related polymethylenetetramines. Chain length and substituent effects on M-2 muscarinic receptor blocking activity

  摘要：

  Several polymethylene tetraamines related to methoctramine (1) were prepared and evaluated for their blocking activity on M-2 muscarinic receptors in guinea pig atria and ileum. It turned out that antimuscarinic potency depends on the following parameters: (a) nature of the substituent on both inner and outer nitrogens and (b) carbon chain length separating the inner nitrogens as well as the inner and outer nitrogens. Optimum activity at cardiac M-2 muscarinic receptors was associated with the chain lengths present in 1, that is, eight methylenes between the inner nitrogens and six methylenes between the inner and outer nitrogens. With regard to the substituents, replacement of the benzylic moiety of 1 by a 2-furyl or a 5-methyl-2-furyl nucleus resulted in enhanced potency toward cardiac M-2 muscarinic receptors. In fact, furtramine (18) and mefurtramine (19) proved to be more potent and more selective than 1. Moreover, N-methylation of the four nitrogens of 1 gave different effects: methylation of the outer nitrogens, giving 22, caused a significant decrease in activity whereas methylation of the inner nitrogens, yielding 23, resulted in an increase in activity in both atria and ileum.

  DOI：

  10.1021/jm00121a017
• 作为产物：
  描述：

  N,N'-((octane-1,8-diylbis(azanediyl))bis(6-oxohexane-6,1-diyl))bis(2-methoxybenzamide) 在 lithium aluminium tetrahydride 作用下， 以 二乙二醇二甲醚 为溶剂， 以62%的产率得到methoctramine
  参考文献：
  名称：

  四胺的合成和选择性 M-胆碱阻断活性。第二部分

  摘要：

  已证明这些物质对胆碱受体 [I] 的 M2 亚型具有选择性亲和力，并且已确定至少一种合成化合物 [XIII: Ar=Ph, A=(CH2)6, B = 1, 4-C6H4(CH2)2] 与甲胺丁胺 [At = 2-MeOC6H4, A = (CH2)6, B = (CHE)s] 相比具有更高的选择性，被认为是该类型中最有前途的制剂 [2] . 这项工作的目的是获得新的四胺 I，其中基团 B 的部分亚甲基被氧原子取代。预计这种取代将显着改变初始化合物的性质。分子极性和亲水性的增加必须改变它们的构象特性，从而改变化合物的生物活性（包括对某些亚型 M-胆碱受体的特异性）。

  DOI：

  10.1007/bf02464370

文献信息

• COMBINATION THERAPY USING A BETA 3 ADRENERGIC RECEPTOR AGONISTS AND AN ANTIMUSCARINIC AGENT
  申请人：Edmondson Scott D.

  公开号：US20120202819A1

  公开（公告）日：2012-08-09

  Described herein is an improved method of treating overactive bladder, wherein the method comprises administering to a patient in need thereof a beta 3 adrenergic receptor agonist, an antimuscarinic agent, and an optional selective M 2 antagonist. Such combination therapy provides improved efficacy and/or reduced side effects.

  本文描述了一种改进的治疗过度活跃膀胱的方法，其中该方法包括向需要治疗的患者施用β3肾上腺素能受体激动剂、抗胆碱药物和可选的选择性M2拮抗剂。这种联合治疗提供了更好的疗效和/或减少了副作用。
• MUSCARINIC COMBINATION OF A SELECTIVE M2-ANTAGONIST AND A PERIPHERAL NON-SELECTIVE ANTAGONIST FOR TREATING HYPOCHOLINERGIC DISORDERS
  申请人：Chase Pharmaceuticals Corporation

  公开号：EP3324966A1

  公开（公告）日：2018-05-30
• Screening Method
  申请人：Komatsu Hidetoshi

  公开号：US20090069228A1

  公开（公告）日：2009-03-12

  The present invention provides compounds or their salts that promote or inhibit the activities of a protein comprising the same or substantially the same as the amino acid sequence represented by SEQ ID NO: 1, compounds or their salts that promote or inhibit the activities of a gene for said protein, antisense polynucleotides comprising the whole or part of a base sequence complimentary or substantially complimentary to the base sequence of a polynucleotide encoding said protein or its partial peptide, antibodies to said protein, etc. These compounds or their salts, antisense nucleotides, antibodies, etc. can be used as agents for the prevention/treatment of mental disorders, prolactin-related disorders, etc.
• US7919260B2
  申请人：——

  公开号：US7919260B2

  公开（公告）日：2011-04-05
• [EN] MUSCARINIC COMBINATION OF A SELECTIVE M2-ANTAGONIST AND A PERIPHERAL NON-SELECTIVE ANTAGONIST FOR TREATING HYPOCHOLINERGIC DISORDERS<br/>[FR] COMBINAISON MUSCARINIQUE D'UN ANTAGONISTE SÉLECTIF DU RÉCEPTEUR M2 ET D'UN ANTAGONISTE NON SÉLECTIF PÉRIPHÉRIQUE POUR LE TRAITEMENT DE TROUBLES HYPOCHOLINERGIQUES
  申请人：CHASE PHARMACEUTICALS CORP

  公开号：WO2017015349A1

  公开（公告）日：2017-01-26

  A combination of a muscarinic receptor antagonist consisting of a M2-receptor antagonist and of a non-selective, peripheral anticholinergic agent, and optionally an anticholinesterase inhibitor, and use of the same for treatment of hypocholinergic type disorders such as Alzheimer type dementia, schizophrenia, schizophrenia associated dementia, and schizoaffective disorders.