N-(m-ethylphenyl)-N-methylcyanamide | 137160-25-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(m-ethylphenyl)-N-methylcyanamide
• 英文别名: m-ethylphenyl-N-methylcyanamide；(3-ethylphenyl)-methylcyanamide
• CAS: 137160-25-9
• 化学式: C₁₀H₁₂N₂
• 分子量: 160.219
• InChiKey: JZPLZDDBGXHLIM-UHFFFAOYSA-N

物化性质

• 沸点：
  304.5±21.0 °C(Predicted)
• 密度：
  1.042±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methylsulfanyl-aniline; hydrochloride 、 N-(m-ethylphenyl)-N-methylcyanamide 以 氯苯 为溶剂， 以61%的产率得到1-(3-Ethylphenyl)-1-methyl-2-(3-methylsulfanylphenyl)guanidine;hydrochloride
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(2,5-Disubstituted phenyl)-N‘-(3-substituted phenyl)-N‘-methylguanidines As N-Methyl-d-aspartate Receptor Ion-Channel Blockers

  摘要：

  In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both a receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (27b, R-2 = R-5 = Br, R-3 = C2H5) exhibited potency at both a receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R-2 and R-5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5-(methylthio)phenyl)-N'-(3-ethylphenyl)- N'-methylguanidine (34b, R-2 = Br, R-5 = SMe, R-3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R-3. Optimal activity in this series are afforded by 43b and 44b (R-2 = Cl or Br, R-5 = R-3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (K-i vs [H-3]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure-activity relationships for-these compounds at the NMDA receptor ion-channel site are discussed.

  DOI：

  10.1021/jm970459c
• 作为产物：
  描述：

  m-ethylphenylcyanamide 以60的产率得到N-(m-ethylphenyl)-N-methylcyanamide
  参考文献：
  名称：

  [EN] PREPARATION OF SUBSTITUTED GUANIDINES

  摘要：

  一种通过在路易斯酸催化剂的存在下，将取代的氰胺与氨或取代胺反应制备取代的胍的方法。还揭示了一种通过将单取代的氰胺与双取代的胺反应制备三取代的胍的方法。

  公开号：

  WO1993019042A1

文献信息

• Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: a new, selective noncompetitive NMDA receptor antagonist
  作者：N. L. Reddy、Lain-Yen Hu、R. E. Cotter、J. B. Fischer、W. J. Wong、R. N. McBurney、E. Weber、D. L. Holmes、S. T. Wong

  DOI：10.1021/jm00028a009

  日期：1994.1

  hylguanidine (40) showed high affinity for the NMDA receptor ion channel site (IC50 = 36 nM vs [3H]-3) and low affinity for sigma receptors (IC50 = 2540 nM vs [3H]-5). Selectivity for the NMDA receptor ion channel sites over sigma receptors appears to be dependent upon the structure of the additional substituents on the guanidine nitrogen atoms bearing the aryl groups. Methyl and ethyl substituents

  作为NMDA受体离子通道位点配体的二芳基胍代表了一类潜在的神经保护药物。合成了与N，N'-二邻甲苯基胍（DTG）（一种已知的选择性sigma受体配体）结构相关的几种二芳基胍，并使用NMDA受体在大鼠或豚鼠脑膜匀浆中进行了体外放射性配体置换试验，并进行了评估。离子通道位点特异性放射性配体[3H]-（+）-5（S）-甲基-10（R），11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺（MK-801，3 ），以及sigma受体特异性放射性配体[3H]-二邻甲苯基胍（DTG，5）。本文介绍了导致新的三和四取代的胍的结构-活性关系，其对NMDA受体离子通道位点具有高选择性，对sigma受体的亲和力弱或微不足道。对称取代的二苯基胍的体外结合结果表明，在苯环上具有邻或间取代基（相对于胍氮的位置）的化合物与对位取代的衍生物相比，对NMDA受体离子通道位点的亲和力更高。在针对对称二芳基胍研究的一组环取
• Tri- and tetra-substituted guanidines and their use as excitatory amino
  申请人：State of Oregon

  公开号：US05262568A1

  公开（公告）日：1993-11-16

  Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

  三取代和四取代的胍基化合物，对苯环异氰酸酯（PCP）受体具有高结合亲和力，且更倾向于对脑内sigma受体具有低亲和力。这些胍基衍生物作为NMDA受体的非竞争性抑制剂，通过作用于NMDA受体离子通道复合物的阻滞剂，从而阻止谷氨酸诱导的NMDA受体反应。这些化合物因此具有神经保护作用，并可用于治疗缺氧、低血糖、脑或脊髓缺血、脑或脊髓创伤以及癫痫、阿尔茨海默病、肌萎缩性侧索硬化症、帕金森病、亨廷顿病、唐氏综合征、科萨科夫病和其他神经退行性疾病的治疗。
• Tri-and tetra-substituted guanidines and their use as excitatory amino
  申请人：State of Oregon, acting by and through the Oregon State Board of Higher

  公开号：US05767162A1

  公开（公告）日：1998-06-16

  Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

  三取代和四取代的胍基化合物具有高结合亲和力，可与苯环哌啶（PCP）受体结合，并更倾向于低亲和力与大脑西格玛受体结合。这些胍基衍生物作为非竞争性抑制剂，通过阻断NMDA受体离子通道复合物的离子通道作用，从而抑制谷氨酸诱导的NMDA受体反应。这些化合物因此具有神经保护作用，并可用于治疗缺氧、低血糖、脑或脊髓缺血、脑或脊髓创伤以及癫痫、阿尔茨海默病、肌萎缩性侧索硬化、帕金森病、亨廷顿病、唐氏综合症、科萨科夫病和其他神经退行性疾病的治疗。
• Tri-and tetra-substituted guanidines and their use as excitatory amino acid antagonists
  申请人：State of Oregon, acting by and through the Oregon State Board of Higher Education, acting for and on behalf of the Oregon Health Sciences University and the University of Oregon

  公开号：US06251948B1

  公开（公告）日：2001-06-26

  Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.

  三取代和四取代的胍基化合物具有高结合亲和力，可以结合到苯环环庚啡（PCP）受体，更好的是，这些化合物对大脑σ受体的亲和力较低。这些胍基衍生物作为非竞争性抑制剂，通过作为NMDA受体离子通道复合物的通道阻滞剂，来抑制谷氨酸诱导的NMDA受体响应。因此，这些化合物具有神经保护作用，并可用于治疗缺氧、低血糖、脑或脊髓缺血、脑或脊髓创伤以及癫痫、阿尔茨海默病、肌萎缩性侧索硬化症、帕金森病、亨廷顿病、唐氏综合症、科萨科夫氏综合症和其他神经退行性疾病的治疗。
• Therapeutic substituted guanidines
  申请人：Cambridge NeuroScience, Inc.

  公开号：US06147063A1

  公开（公告）日：2000-11-14

  The present invention provides therapeutically useful substituted guanidines of the following Formula: ##STR1## and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such guanidines.

  本发明提供了以下式子的治疗上有用的取代胍类：##STR1## 以及利用或包含其中一种或多种胍类的治疗方法和制药组合物。