ethyl (E)-(indol-5-yl)-2-butenoate | 146327-25-5

• 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)-(indol-5-yl)-2-butenoate
• 英文别名: ethyl 3-(indol-5-yl)isocrotonate；ethyl (E)-3-(1H-indol-5-yl)but-2-enoate
• CAS: 146327-25-5
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: AUQYKMOBDWTUCI-CSKARUKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl (E)-(indol-5-yl)-2-butenoate 在 lithium hydroxide 、 sodium hydroxide 、 三正丁胺 、 2-chloromethylpyridinium iodide 、 potassium tert-butylate 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 8.5h， 生成 4-{2-[(E)-3-(1-Pentyl-1H-indol-5-yl)-but-2-enoylamino]-phenoxy}-butyric acid
  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 、 磷酰基乙酸三乙酯 在 乙醇 、 sodium hydride 作用下， 生成 ethyl (E)-(indol-5-yl)-2-butenoate
  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 which inhibit steroid 5.alpha. reductase
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05239083A1

  公开（公告）日：1993-08-24

  The present invention provides Indole derivatives represented by the formula (I) ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 independently represent hydrogen or lower alkyl; R.sup.4 represents hydrogen, lower alkyl or cycloalkyl; R.sup.5 represents hydrogen, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, --CHR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 independently represent hydrogen, alkyl, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, --(CH.sub.2).sub.m OR.sup.9 (wherein m is an integer of 1-3 and R.sup.9 is lower alkyl), substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted furyl, or substituted or unsubstituted thienyl], ##STR2## (wherein Y is CH.sub.2, O, S, CH.sub.2 --CH.sub.2, CH.dbd.CH, CH.sub.2 --O or CH.sub.2 --S); R.sup.6 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 salt thereof. The compound shows prominent inhibition effects on steroid 5.alpha.-reductase activity, and are useful in treating benign prostatic hypertrophy, prostate cancer, baldness and acne.

  本发明提供了由式（I）表示的吲哚衍生物，其中R.sup.1、R.sup.2和R.sup.3独立地代表氢或较低的烷基；R.sup.4代表氢、较低的烷基或环烷基；R.sup.5代表氢、取代或未取代的环烷基、取代或未取代的环烯基、--CHR.sup.7 R.sup.8（其中R.sup.7和R.sup.8独立地代表氢、烷基、烯基、炔基、取代或未取代的环烷基、--(CH.sub.2).sub.m OR.sup.9（其中m为1-3的整数，R.sup.9为较低的烷基）、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或取代或未取代的噻吩基），##STR2##（其中Y为CH.sub.2、O、S、CH.sub.2 --CH.sub.2、CH.dbd.CH、CH.sub.2 --O或CH.sub.2 --S）；R.sup.6代表氢、较低的烷基或较低的烷氧基或卤素；X代表O或S(O)q（其中q为0-2的整数）；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5α-还原酶活性具有显著的抑制作用，并可用于治疗良性前列腺增生、前列腺癌、秃头和痤疮。
• 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).