1-[2-[(2R)-oxiran-2-yl]ethyl]-3-phenyl-2lambda6,1,3-benzothiadiazole 2,2-dioxide | 1033227-50-7

• 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: 1-[2-[(2R)-oxiran-2-yl]ethyl]-3-phenyl-2lambda6,1,3-benzothiadiazole 2,2-dioxide
• 英文别名: 1-[2-[(2R)-oxiran-2-yl]ethyl]-3-phenyl-2λ6,1,3-benzothiadiazole 2,2-dioxide
• CAS: 1033227-50-7
• 化学式: C₁₆H₁₆N₂O₃S
• 分子量: 316.381
• InChiKey: XIUWFXQQRPCQJU-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-[(2R)-oxiran-2-yl]ethyl]-3-phenyl-2lambda6,1,3-benzothiadiazole 2,2-dioxide 、 甲胺 以 乙醇 为溶剂， 反应 0.05h， 生成 (2R)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-1-(methylamino)butan-2-ol
  参考文献：
  名称：

  Discovery of Novel Selective Norepinephrine Reuptake Inhibitors: 4-[3-Aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231)

  摘要：

  Structural modification of a virtual screening hit led to the identification of a new series of 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols which are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound S-17b (WYE-103231) had low nanomolar hNET potency (IC(50) = 1.2 nM) and excellent selectivity for hNET over hsERT (> 1600-fold) and hDAT (> 600-fold). S-17b additionally had a good pharmacokinetic profile and demonstrated oral efficacy in rat models of ovariectomized-induced thermoregulatory dysfunction and morphine dependent flush as well as the hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain.

  DOI：

  10.1021/jm100053t
• 作为产物：
  描述：

  1-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide 、 (R)-4-甲苯磺酰氧基-1,2-环氧基丁烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 1-[2-[(2R)-oxiran-2-yl]ethyl]-3-phenyl-2lambda6,1,3-benzothiadiazole 2,2-dioxide
  参考文献：
  名称：

  Discovery of Novel Selective Norepinephrine Reuptake Inhibitors: 4-[3-Aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231)

  摘要：

  Structural modification of a virtual screening hit led to the identification of a new series of 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols which are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound S-17b (WYE-103231) had low nanomolar hNET potency (IC(50) = 1.2 nM) and excellent selectivity for hNET over hsERT (> 1600-fold) and hDAT (> 600-fold). S-17b additionally had a good pharmacokinetic profile and demonstrated oral efficacy in rat models of ovariectomized-induced thermoregulatory dysfunction and morphine dependent flush as well as the hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain.

  DOI：

  10.1021/jm100053t

文献信息

• Discovery of Novel Selective Norepinephrine Reuptake Inhibitors: 4-[3-Aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3<i>H</i>)-yl]-1-(methylamino)butan-2-ols (WYE-103231)
  作者：David J. O’Neill、Adedayo Adedoyin、Peter D. Alfinito、Jenifer A. Bray、Scott Cosmi、Darlene C. Deecher、Andrew Fensome、Jim Harrison、Liza Leventhal、Charles Mann、Casey C. McComas、Nicole R. Sullivan、Taylor B. Spangler、Albert J. Uveges、Eugene J. Trybulski、Garth T. Whiteside、Puwen Zhang

  DOI：10.1021/jm100053t

  日期：2010.6.10

  Structural modification of a virtual screening hit led to the identification of a new series of 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols which are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound S-17b (WYE-103231) had low nanomolar hNET potency (IC(50) = 1.2 nM) and excellent selectivity for hNET over hsERT (> 1600-fold) and hDAT (> 600-fold). S-17b additionally had a good pharmacokinetic profile and demonstrated oral efficacy in rat models of ovariectomized-induced thermoregulatory dysfunction and morphine dependent flush as well as the hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain.