ethyl (E)-3-(1-pentylindol-5-yl)but-2-enoate | 146328-17-8

• 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: ethyl (E)-3-(1-pentylindol-5-yl)but-2-enoate
• CAS: 146328-17-8
• 化学式: C₁₉H₂₅NO₂
• 分子量: 299.413
• InChiKey: WMTLVBBQPOCQPN-FYWRMAATSA-N

物化性质

• 沸点：
  437.4±14.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl (E)-3-(1-pentylindol-5-yl)but-2-enoate 在 lithium hydroxide 、 三正丁胺 、 2-chloromethylpyridinium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-{2-[(E)-3-(1-Pentyl-1H-indol-5-yl)-but-2-enoylamino]-phenoxy}-butyric acid ethyl ester
  参考文献：
  名称：

  (E)-4-{2-[[3-(Indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric Acid Derivatives: A New Class of Steroid 5.alpha.-Reductase Inhibitors in the Rat Prostate. 1

  摘要：

  A series of (E)-4-{2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyI or benzyl substituent of proper size at position I of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2-butenyl]amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).

  DOI：

  10.1021/jm00015a011
• 作为产物：
  描述：

  5-乙酰吲哚 在 乙醇 、 potassium tert-butylate 、 sodium hydride 作用下， 反应 10.5h， 生成 ethyl (E)-3-(1-pentylindol-5-yl)but-2-enoate
  参考文献：
  名称：

  (E)-4-{2-[[3-(Indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric Acid Derivatives: A New Class of Steroid 5.alpha.-Reductase Inhibitors in the Rat Prostate. 1

  摘要：

  A series of (E)-4-{2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyI or benzyl substituent of proper size at position I of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2-butenyl]amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).

  DOI：

  10.1021/jm00015a011

文献信息

• Indole derivatives
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP0511477A1

  公开（公告）日：1992-11-04

  The present invention provides Indole derivatives represented by the formula (I) wherein R¹, R² and R³ independently represent hydrogen or lower alkyl; R⁴ represents hydrogen, lower alkyl or cycloalkyl; R⁵ represents hydrogen, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, -CHR⁷R⁸ where R⁷ and R⁸ independently represent hydrogen, alkyl, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, -(CH₂)mOR⁹ (wherein m is an integer of 1 - 3 and R⁹ is lower alkyl), substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted furyl, or substituted or unsubstituted thienyl], (wherein p is an integer of 1 - 3) or (wherein Y is CH₂, O, S, CH₂-CH₂, CH=C, CH₂-O or CH₂-S); R⁶ represents hydrogen, lower alkyl or lower alkoxy or halogen; X represents O or S(O)q (wherein q is an integer of 0-2); and n represents an integer of 1-6} or pharmaceutically acceptable salts thereof. The compound shows prominent inhibition effects on steroid 5 α-reductase activity, and are useful in treating benign prostatic hypertrophy, prostate cancer, baldness and acne.

  本发明提供了式 (I) 所代表的吲哚衍生物 其中 R¹、R² 和 R³ 独立地代表氢或低级烷基； R⁴ 代表氢、低级烷基或环烷基； R⁵ 代表氢、取代或未取代的环烷基、取代或未取代的环烯基、-CHR⁷R⁸ 其中 R⁷ 和 R⁸ 独立地代表氢、烷基、烯基、炔基、取代或未取代的环烷基、-(CH₂)mOR⁹（其中 m 为 1-3 的整数，R⁹ 为低级烷基）、取代或未取代的芳基、取代或未取代的吡啶基、取代或未取代的呋喃基、取代或未取代的噻吩基]、 (其中 p 为 1 - 3 的整数）或 (其中 Y 是 CH₂、O、S、CH₂-CH₂、CH=C、CH₂-O 或 CH₂-S）； R⁶ 代表氢、低级烷基或低级烷氧基或卤素； X 代表 O 或 S(O)q（其中 q 为 0-2 的整数）； 和 n 代表 1-6 的整数}或其药学上可接受的盐。 该化合物对类固醇 5 α-还原酶活性有显著的抑制作用，可用于治疗良性前列腺肥大、前列腺癌、秃头和痤疮。
• US5239083A
  申请人：——

  公开号：US5239083A

  公开（公告）日：1993-08-24
• (E)-4-{2-[[3-(Indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric Acid Derivatives: A New Class of Steroid 5.alpha.-Reductase Inhibitors in the Rat Prostate. 1
  作者：Toshiaki Kumazawa、Hitoshi Takami、Nobuyuki Kishibayashi、Akio Ishii、Yoshitomo Nagahara、Noriaki Hirayama、Hiroyuki Obase

  DOI：10.1021/jm00015a011

  日期：1995.7

  A series of (E)-4-2-[[3-(indol-5-yl)-1-oxo-2-butenyl]amino]phenoxy}butyric acid derivatives was prepared, and the derivatives were demonstrated to be potent inhibitors of steroid 5 alpha-reductase in the rat prostate. The structure-activity relationships were as follows. An alpha-branched alkyI or benzyl substituent of proper size at position I of the indole is crucial for optimal enzyme inhibitory activity. N-Methylation of the amide NH resulted in complete loss of activity. Thus, coplanarity of the benzene ring and amide moiety is essential for such activity. Among the compounds prepared, (E)-4-(2-[[3-[1-[bis(4-fluorophenyl)methyl]indol-5-yl]-1-oxo-2-butenyl]amino]phenoxy)butyric acid (57, KF18678) was one of the most potent compounds (rat prostate 5 alpha-reductase IC50 = 3.3 nM).