(S)-3-phenyl-N-[1-(3-hydroxyphenyl)ethyl]acrylamide | 477313-06-7

• 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: (S)-3-phenyl-N-[1-(3-hydroxyphenyl)ethyl]acrylamide
• 英文别名: (E)-N-[(1S)-1-(3-hydroxyphenyl)ethyl]-3-phenylprop-2-enamide
• CAS: 477313-06-7
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: QBIJTRNQJZQZST-NHAQELONSA-N

物化性质

• 沸点：
  529.6±50.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-3-phenyl-N-[1-(3-hydroxyphenyl)ethyl]acrylamide 在 吡啶 、 potassium phosphate 、 tris(dibenzylideneacetone)dipalladium (0) 、 2-(二叔丁基膦)联苯 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 (S)-3-Phenyl-N-[1-(3-morpholin-4-yl-phenyl)ethyl]acrylamide
  参考文献：
  名称：

  (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide:  An Orally Bioavailable KCNQ2 Opener with Significant Activity in a Cortical Spreading Depression Model of Migraine

  摘要：

  (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.

  DOI：

  10.1021/jm034073f
• 作为产物：
  描述：

  (S)-(-)-1-(3-甲氧基苯基)乙胺 在 4-二甲氨基吡啶 、 三溴化硼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 (S)-3-phenyl-N-[1-(3-hydroxyphenyl)ethyl]acrylamide
  参考文献：
  名称：

  (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide:  An Orally Bioavailable KCNQ2 Opener with Significant Activity in a Cortical Spreading Depression Model of Migraine

  摘要：

  (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.

  DOI：

  10.1021/jm034073f

文献信息

• Cinnamide derivatives as KCNQ potassium channel modulators
  申请人：——

  公开号：US20030166650A1

  公开（公告）日：2003-09-04

  There is provided novel cinnamide derivatives of Formula I 1 wherein R is C 1-4 alkyl or trifluoromethyl; R 1 is selected from the group consisting of pyridinyl, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, phenyl and substituted phenyl in which said substituted phenyl is substituted with one or two substituents each independently selected-from the group consisting of halogen, C 1-4 alkyl, C 1-4 alkoxy, trifluoromethyl, trifluoromethoxy and nitro; R 2 and R 3 are each independently selected from the group consisting of hydrogen, C 1-4 alkyl, and halogen; R 4 is selected from the group consisting of di(C 1-4 alkyl)amino, trifluoromethoxy and optionally substituted morpholin-4-yl, pyridinyl, pyrimidinyl, piperazinyl, and pyrazinyl with one or two substituents in which said substituent is independently selected from the group consisting of C 1-4 alkyl, aminomethyl, hydroxymethyl, chloro or fluoro; R 5 is hydrogen, chloro or fluoro; or R 4 and R 5 taken together are —CH═CH—CH═CH— or —X(CH 2 ) m Y— in which X and Y are each independently selected from the group consisting of CH 2 , (CH 2 ) n N(R 9 )— and O, wherein m is 1 or 2; n is 0 or 1; and R 6 , R 7 , and R 8 are each independently selected from hydrogen, chloro and fluoro; and R 9 is selected from the group consisting of hydrogen, C 1-4 alkyl, hydroxyethyl, C 1-4 alkoxyethyl, cyclopropylmethyl, —CO 2 (C 1-4 alkyl), and —CH 2 CH 2 NR 10 R 11 in which R 10 and R 11 are each independently hydrogen or C 1-4 alkyl, which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.

  提供了一种新型的 Formula I1 中的肉桂酰胺衍生物，其中 R 为 C1-4 烷基或三氟甲基；R1 选自吡啶基、喹啉基、噻吩基、呋喃基、1,4-苯并二氧杂基、1,3-苯并二氧杂基、色基、茚基、联苯基、苯基和取代苯基，其中所述取代苯基取代有一个或两个取代基，每个取代基独立地选自卤素、C1-4 烷基、C1-4 烷氧基、三氟甲基、三氟甲氧基和硝基；R2 和 R3 各自独立地选自氢、C1-4 烷基和卤素；R4 选自二(C1-4 烷基)氨基、三氟甲氧基和可选取代的吗啉-4-基、吡啶基、嘧啶基、哌嗪基和吡嗪基，其中所述基带有一个或两个取代基，所述取代基独立地选自 C1-4 烷基、氨甲基、羟甲基、氯或氟；R5 为氢、氯或氟；或者 R4 和 R5 结合成 —CH═CH—CH═CH— 或 —X(CH2)mY—，其中 X 和 Y 各自独立地选自 CH2、(CH2)nN(R9)— 和 O，其中 m 为 1 或 2；n 为 0 或 1；R6、R7 和 R8 各自独立地选自氢、氯和氟；R9 选自氢、C1-4 烷基、羟乙基、C1-4 烷氧乙基、环丙基甲基、—CO2(C1-4 烷基) 和 —CH2CH2NR10R11，其中 R10 和 R11 各自独立地为氢或 C1-4 烷基，这些化合物是 KCNQ 钾通道的开放剂，可用于治疗对 KCNQ 钾通道的开放有反应的疾病。
• [EN] CINNAMIDE DERIVATIVES AS KCNQ POTASSIUM CHANNEL MODULATORS<br/>[FR] DERIVES DE LA CINNAMIDE MODULATEURS DU CANAL POTASSIQUE KCNQ
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2002096858A1

  公开（公告）日：2002-12-05

  There is provided novel cinnamide derivatives of Formula I wherein R is C1-4 alkyl or trifluoromethyl, R1 is selected from the group consisting of pyridinyl, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, phenyl and substituted phenyl which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.

  提供了一种新的苯甲酰胺衍生物，其化学式为I，其中R为C1-4烷基或三氟甲基，R1选自吡啶基，喹啉基，噻吩基，呋喃基，1,4-苯并二氧杂环基，1,3-苯并二氧杂环基，色甘醇基，茚基，联苯基，苯基和取代苯基，这些化合物是KCNQ钾通道的开放剂，可用于治疗对KCNQ钾通道的开放反应的疾病。
• CINNAMIDE DERIVATIVES AS KCNQ POTASSIUM CHANNEL MODULATORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1392644A1

  公开（公告）日：2004-03-03
• US6831080B2
  申请人：——

  公开号：US6831080B2

  公开（公告）日：2004-12-14
• (<i>S</i>)-<i>N</i>-[1-(3-Morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide:  An Orally Bioavailable KCNQ2 Opener with Significant Activity in a Cortical Spreading Depression Model of Migraine
  作者：Yong-Jin Wu、Christopher G. Boissard、Corinne Greco、Valentin K. Gribkoff、David G. Harden、Huan He、Alexandre L'Heureux、Shing Hong Kang、Gene G. Kinney、Ronald J. Knox、Joanne Natale、Amy E. Newton、Sanna Lehtinen-Oboma、Michael W. Sinz、Digavalli V. Sivarao、John E. Starrett,、Li-Qiang Sun、Svetlana Tertyshnikova、Mark W. Thompson、David Weaver、Henry S. Wong、Lei Zhang、Steven I. Dworetzky

  DOI：10.1021/jm034073f

  日期：2003.7.1

  (S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.