(2R)-N-(5-bromo-1,3,4-thiadiazol-2-yl)-1-(4-chlorophenyl)sulfonylpiperidine-2-carboxamide | 1415488-73-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-N-(5-bromo-1,3,4-thiadiazol-2-yl)-1-(4-chlorophenyl)sulfonylpiperidine-2-carboxamide
• CAS: 1415488-73-1
• 化学式: C₁₄H₁₄BrClN₄O₃S₂
• 分子量: 465.779
• InChiKey: JEWDJFLVINCHCE-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R)-N-(5-bromo-1,3,4-thiadiazol-2-yl)-1-(4-chlorophenyl)sulfonylpiperidine-2-carboxamide 、 4-甲氧基苯硼酸 在 potassium phosphate 、 palladium diacetate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (2R)-1-(4-chlorophenyl)sulfonyl-N-[5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl]piperidine-2-carboxamide
  参考文献：
  名称：

  Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator

  摘要：

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.060
• 作为产物：
  描述：

  (R)-piperidine-2-carboxylic acid 、 2-氨基-5-溴-1,3,4-噻二唑 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2R)-N-(5-bromo-1,3,4-thiadiazol-2-yl)-1-(4-chlorophenyl)sulfonylpiperidine-2-carboxamide
  参考文献：
  名称：

  Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator

  摘要：

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.060

文献信息

• Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator
  作者：Margrith E. Mattmann、Haibo Yu、Zhihong Lin、Kaiping Xu、Xiaofang Huang、Shunyou Long、Meng Wu、Owen B. McManus、Darren W. Engers、Uyen M. Le、Min Li、Craig W. Lindsley、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2012.07.060

  日期：2012.9

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.