N-[4-[[(2S)-oxiran-2-yl]methoxy]phenyl]methanesulfonamide | 392620-41-6

• 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: N-[4-[[(2S)-oxiran-2-yl]methoxy]phenyl]methanesulfonamide
• 英文别名: (S)-Glycidyl N-Methylsulfonyl-p-Aminophenyl Ether
• CAS: 392620-41-6
• 化学式: C₁₀H₁₃NO₄S
• 分子量: 243.284
• InChiKey: DMBDRKKEZLXIBV-SNVBAGLBSA-N

物化性质

• 沸点：
  402.7±51.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  对羟基苯乙胺 、 N-[4-[[(2S)-oxiran-2-yl]methoxy]phenyl]methanesulfonamide 以 乙醇 为溶剂， 以61%的产率得到(S)-1-(4-methanesulfonamidophenoxy)-3-(4-hydroxyphenylethylamino)-2-propanol
  参考文献：
  名称：

  Enantiomeric Propanolamines as selective N-Methyl-d-aspartate 2B Receptor Antagonists

  摘要：

  Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.

  DOI：

  10.1021/jm8002153
• 作为产物：
  描述：

  对硝基苯酚 在 5%-palladium/activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 cesium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 28.25h， 生成 N-[4-[[(2S)-oxiran-2-yl]methoxy]phenyl]methanesulfonamide
  参考文献：
  名称：

  NMDA RECEPTOR ANTAGONISTS FOR NEUROPROTECTION

  摘要：

  公开号：

  EP2170334B1

文献信息

• Heterocyclic beta-3 adrenergic receptor agonists
  申请人：American Home Products Corporation

  公开号：US20020028832A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 U, V, W, X, and Y are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  这项发明提供了具有结构式I的化合物 1 其中U、V、W、X和Y如前文所定义， 或其药学上可接受的盐，用于治疗或抑制与胰岛素抵抗或高血糖相关的代谢紊乱（通常与肥胖或葡萄糖不耐受有关）、动脉粥样硬化、胃肠道疾病、神经炎症、青光眼、眼压增高和频繁排尿；特别适用于治疗或抑制2型糖尿病。
• Synthesis and evaluation of novel phenoxypropanolamine derivatives containing acetanilides as potent and selective β3-adrenergic receptor agonists
  作者：Tatsuya Maruyama、Kenichi Onda、Masahiko Hayakawa、Norio Seki、Takumi Takahashi、Hiroyuki Moritomo、Takayuki Suzuki、Tetsuo Matsui、Toshiyuki Takasu、Itsuro Nagase、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2009.03.044

  日期：2009.5

  In the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of phenoxypropanolamine derivatives containing acetanilides were prepared and their biological activities were evaluated at the human β3-, β2-, and β1-ARs. Several of the analogues (21a, 21b, and 27a) exhibited

  在寻找有效和选择性的人β3-肾上腺素能受体（AR）激动剂作为治疗肥胖和非胰岛素依赖型（II型）糖尿病的潜在药物时，制备了一系列新的含乙酰苯胺的苯氧基丙醇胺衍生物，并对其生物学活性进行了评估。在人类β3-，β2-和β1-ARs中。几个类似物（21a，21b和27a）在β3-AR上显示出强大的激动活性。在本文所述的化合物中，发现N-甲基-1-苄基咪唑-2-基乙酰苯胺衍生物（21b）是最有效和选择性最强的β3-AR激动剂，EC 50β1-或β2-AR的值仅为0.28μM，且无激动活性。另外，在啮齿动物糖尿病模型中21b显示出显着的降血糖活性。
• A Glutamate <i>N</i>-Methyl-d-Aspartate (NMDA) Receptor Subunit 2B–Selective Inhibitor of NMDA Receptor Function with Enhanced Potency at Acidic pH and Oral Bioavailability for Clinical Use
  作者：Scott J. Myers、Kamalesh P. Ruppa、Lawrence J. Wilson、Yesim A. Tahirovic、Polina Lyuboslavsky、David S. Menaldino、Zackery W. Dentmon、George W. Koszalka、Robert Zaczek、Raymond J. Dingledine、Stephen F. Traynelis、Dennis C. Liotta

  DOI：10.1124/jpet.120.000370

  日期：2021.10

  extracellular acidic pH values relative to physiologic pH. This property should render these compounds more effective inhibitors of N-methyl-d-aspartate receptors at synapses responding to a high frequency of action potentials, since glutamate-containing vesicles are acidic within their lumen. In addition, acidification of penumbral regions around ischemic tissue should also enhance selective drug action for

  我们描述了来自一系列新的谷氨酸N-甲基-d-天冬氨酸受体亚基 2B 选择性抑制剂的临床候选分子，该抑制剂在相对于生理 pH 值的细胞外酸性 pH 值下显示出增强的抑制作用。这种性质应该使这些化合物成为更有效的N-甲基-d抑制剂突触处的天冬氨酸受体对高频率的动作电位作出反应，因为含谷氨酸的囊泡在其管腔内是酸性的。此外，缺血组织周围半影区域的酸化也应增强选择性药物作用以改善神经保护。我们在此描述的芳基哌嗪在临床前研究中显示出强大的神经保护作用和最小的副作用。临床候选分子 NP10679 具有高口服生物利用度和良好的脑穿透性，适用于静脉和口服给药，用于人体治疗。
• Ph-dependent nmda receptor antagonists
  申请人：——

  公开号：US20040138502A1

  公开（公告）日：2004-07-15

  NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neuroprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower-than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia tat may occur during cardiac surgery, hypoxia tat may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chronic pain, vascular dementia and glioma tumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Preferably the compounds provided herein are allosteric NMDA inhibitors.

  NMDA受体阻滞剂，包括pH敏感的NMDA受体阻滞剂，被提供作为神经保护药物，可用于中风、创伤性脑损伤、癫痫和其他涉及大脑或脊髓组织酸化的神经事件。本发明的组合物和方法用于治疗由NMDA受体激活引起的神经退行性疾病。所述化合物在具有低于正常pH的脑组织中具有增强的活性，这是由于病理条件（如中风引起的低氧血症、创伤性脑损伤、在心脏手术期间可能发生的全局缺血、呼吸停止后可能发生的低氧血症、妊娠期高血压综合症、脊髓损伤、癫痫、慢性疼痛、血管性痴呆和胶质瘤等）。所述化合物也可用于预防帕金森病、阿尔茨海默病、亨廷顿舞蹈症、肌萎缩侧索硬化症和其他已知对使用NMDA受体阻滞剂治疗有反应的神经退行性疾病患者的神经退行性。优选地，本文提供的化合物是变构NMDA抑制剂。
• PH-dependent NMDA receptor antagonists
  申请人：Traynelis Stephen F.

  公开号：US20090023791A1

  公开（公告）日：2009-01-22

  NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neurprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia that may occur during cardiac surgery, hypoxia that may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chrounic pain, vascular dementia and glioma rumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Prefebably the compounds provided herein are allosteric NMDA inhibitors.

  NMDA受体阻滞剂，包括pH敏感的NMDA受体阻滞剂，作为神经保护药物提供，可用于中风、创伤性脑损伤、癫痫和其他涉及脑或脊髓组织酸化的神经事件。本发明的组合物和方法用于治疗由NMDA受体激活引起的神经退行性疾病。所述化合物在具有低于正常pH的脑组织中具有增强的活性，这是由于病理情况（如中风、创伤性脑损伤、可能发生于心脏手术期间的全球性缺血、呼吸停止后可能发生的低氧、先兆子痫、脊髓损伤、癫痫、慢性疼痛、血管性痴呆和胶质瘤）所致。所述化合物还可用于预防帕金森病、阿尔茨海默病、亨廷顿舞蹈症、肌萎缩侧索硬化症和其他已知对使用NMDA受体阻滞剂治疗有响应的神经退行性疾病患者的神经退行性。最好所提供的化合物是变构的NMDA抑制剂。