4-carbethoxycinnamic acid | 105080-14-6

• 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: 4-carbethoxycinnamic acid
• 英文别名: E-(4-Ethoxycarbonyl)benzenepropenoic acid；4-(ethoxycarbonyl)cinnamic acid；(E)-3-(4-ethoxycarbonylphenyl)prop-2-enoic acid
• CAS: 105080-14-6
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: QCEPAZSRRGCQJL-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-carbethoxycinnamic acid 在 chromium(VI) oxide 、 diatomaceous earth 、 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 38.5h， 生成 4-((E)-2-{(S)-2-Methyl-1-[(S)-2-(3,3,3-trifluoro-1-isopropyl-2-oxo-propylcarbamoyl)-pyrrolidine-1-carbonyl]-propylcarbamoyl}-vinyl)-benzoic acid
  参考文献：
  名称：

  Discovery and Biological Activity of Orally Active Peptidyl Trifluoromethyl Ketone Inhibitors of Human Neutrophil Elastase

  摘要：

  Previously we had shown that tripeptidyl trifluoromethyl ketones (TFMKs) possessing an N-terminal diarylacylsulfonamide, such as ICI 200,880 and ICI 200,355, displayed unparalleled protectin against the lung damage induced by human neutrophil elastase (HNE) when the inhibitors were administered intratracheally. Since the diarylacylsulfonamides were designed specifically to afford a long residence time in the lung, it was not unexpected that inhibitors from this class of TFMKs were not active when administered orally. Upon evaluating a large number of peptidyl TFMKs possessing a variety of N-terminal groups, several compounds were identified which demonstrated oral activity. Compounds were evaluated for their oral activity by measuring their ability to inhibit the increase in lung weight relative to body weight (Lw/Bw), the increase in red blood cells, and the increase in white blood cells induced by intratracheally administered HNE (100 mu g/hamster). A number of tripeptidyl trifluoromethyl ketones containing neutral N-terminal groups displayed good oral activity, while those containing basic, acidic, or polar groups did not. Compound 50, possessing an N-terminal 4-(CH3O)C6H4CO group, was particularly effective, reducing Lw/Bw by 77%, red cells by 89%, and white cells by 91% when dosed at 37.5 mg/kg orally. Thus, by modifying the N-terminal group of tripeptidyl TFMKs, inhibitors can be designed which are effective in vivo when administered either orally or intratracheally.

  DOI：

  10.1021/jm960819g

文献信息

• Peptide derivatives
  申请人：ICI Americas Inc.

  公开号：US04910190A1

  公开（公告）日：1990-03-20

  The invention concerns pharmaceutically useful trifluoromethyl ketone substituted di-, tri- and tetra-peptide derivatives of the formulae Ia, Ib, Ic set out hereinafter, and salts thereof, which are inhibitors of human leukocyte elastase. Also described herein are pharmaceutical compositions containing a peptide derivative and processes and intermediates for use in the manufacture of the peptide derivatives.

  本发明涉及具有药用价值的、三氟甲基酮取代的二肽、三肽和四肽衍生物，其结构式为Ia、Ib、Ic，以及它们的盐，这些衍生物是人类白细胞弹性蛋白酶的抑制剂。本文还描述了含有肽衍生物的药物组合物，以及用于制造这些肽衍生物的过程和中间体。
• Quinoline derivatives, processes for their preparation and their use as
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06083959A1

  公开（公告）日：2000-07-04

  A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl, R.sup.2 is hydrogen, lower alkyl or a heterocyclic group, R.sup.3 is hydrogen, lower alkyl or halogen, R.sup.4 is lower alkyl or halogen, R.sup.5 is nitro or amino substituted with substituent(s) selected from the group consisting of lower alkyl and acyl, and A is lower alkylene.

  一种化合物的化学式：##STR1## 其中 R.sup.1 是较低的烷基，R.sup.2 是氢、较低烷基或杂环基，R.sup.3 是氢、较低烷基或卤素，R.sup.4 是较低烷基或卤素，R.sup.5 是硝基或氨基，带有从较低烷基和酰基的取代基选取的取代基，A 是较低的亚烯基。
• HETEROCYCLIC COMPOUNDS AS BRADYKININ ANTAGONISTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0861243B1

  公开（公告）日：2003-11-12
• QUINOLINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION, AND THEIR USE AS MEDICAMENTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0900203A1

  公开（公告）日：1999-03-10
• US4910190A
  申请人：——

  公开号：US4910190A

  公开（公告）日：1990-03-20