(E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-oxohex-2-enamide | 840526-96-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-oxohex-2-enamide
• CAS: 840526-96-7
• 化学式: C₂₄H₂₇NO₄
• 分子量: 393.483
• InChiKey: ZNQWTCBFPUABOH-OBGWFSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  二甲胺 、 (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-oxohex-2-enamide 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 以89%的产率得到(E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-(dimethylamino)hex-2-enamide
  参考文献：
  名称：

  Discovery of Potent, Orally Available Vanilloid Receptor-1 Antagonists. Structure−Activity Relationship of N-Aryl Cinnamides

  摘要：

  The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators: particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1): an antagonist that blocks the capsaicin-induced and pH-induced uptake of Ca-45(2+) in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report.. we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F-oral = 39% and 17%. respectively).

  DOI：

  10.1021/jm049485i
• 作为产物：
  描述：

  乙基3-[4-(2-甲基-2-丙基)苯基]-2-丙炔酸酯 在 盐酸 、 双(乙腈)氯化钯(II) 、 氢氧化钾 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-oxohex-2-enamide
  参考文献：
  名称：

  Discovery of Potent, Orally Available Vanilloid Receptor-1 Antagonists. Structure−Activity Relationship of N-Aryl Cinnamides

  摘要：

  The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators: particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1): an antagonist that blocks the capsaicin-induced and pH-induced uptake of Ca-45(2+) in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report.. we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F-oral = 39% and 17%. respectively).

  DOI：

  10.1021/jm049485i

文献信息

• Discovery of Potent, Orally Available Vanilloid Receptor-1 Antagonists. Structure−Activity Relationship of <i>N</i>-Aryl Cinnamides
  作者：Elizabeth M. Doherty、Christopher Fotsch、Yunxin Bo、Partha P. Chakrabarti、Ning Chen、Narender Gavva、Nianhe Han、Michael G. Kelly、John Kincaid、Lana Klionsky、Qingyian Liu、Vassil I. Ognyanov、Rami Tamir、Xianghong Wang、Jiawang Zhu、Mark H. Norman、James J. S. Treanor

  DOI：10.1021/jm049485i

  日期：2005.1.1

  The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators: particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1): an antagonist that blocks the capsaicin-induced and pH-induced uptake of Ca-45(2+) in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 +/- 5 and 150 +/- 80 nM, respectively. In this report.. we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (F-oral = 39% and 17%. respectively).