2-(2-bromo-4-[(2-oxocyclopentyl)methyl]phenyl)propanoic acid | 1241405-02-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(2-bromo-4-[(2-oxocyclopentyl)methyl]phenyl)propanoic acid
• 英文别名: 2-{2-bromo-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic acid；2-[2-Bromo-4-[(2-oxocyclopentyl)methyl]phenyl]propanoic acid
• CAS: 1241405-02-6
• 化学式: C₁₅H₁₇BrO₃
• 分子量: 325.202
• InChiKey: MGAGJKNDSAFONJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-bromo-4-[(2-oxocyclopentyl)methyl]phenyl)propanoic acid 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of loxoprofen derivatives

  摘要：

  Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-{4'-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.050
• 作为产物：
  描述：

  methyl 2-(2-bromo-4-[(1-methoxycarbonyl-2-oxocyclopentyl)methyl]phenyl)propanoate 在 盐酸 、 水 、 溶剂黄146 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 以80%的产率得到2-(2-bromo-4-[(2-oxocyclopentyl)methyl]phenyl)propanoic acid
  参考文献：
  名称：

  Properties and Synthesis of 2-{2-Fluoro (or Bromo)-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic Acid: Nonsteroidal Anti-inflammatory Drugs with Low Membrane Permeabilizing and Gastric Lesion-Producing Activities

  摘要：

  We previously proposed that membrane permeabilization activity of NSAIDs is involved in NSAID-induced gastric lesions. We here synthesized derivatives of loxoprofen that have lower membrane permeabilization activity than other NSAIDs. Compared to loxoprofen, the derivatives 10a and 10b have lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 10a and 10b are likely to be therapeutically beneficial as safer NSAIDs.

  DOI：

  10.1021/jm101116s

文献信息

• LOXOPROFEN DERIVATIVE AND PHARMACEUTICAL PREPARATION CONTAINING THE SAME
  申请人：Mizushima Toru

  公开号：US20120016158A1

  公开（公告）日：2012-01-19

  There is provided a novel loxoprofen derivative that has no side effect such as a gastrointestinal disorder and also has excellent anti-inflammatory and analgesic effects and is represented by the following formula (I) or (II): (wherein R 1 and R 2 each represent a halogen atom or a substituted or unsubstituted phenyl group) or a pharmacologically acceptable salt thereof. In the derivative, the halogen atom is selected from a chlorine atom, a bromine atom, a fluorine atom, and an iodine atom, and a substituent of the substituted phenyl group is a halogen atom, a hydroxyl group, a substituted or unsubstituted lower alkyl group, a lower alkylthio group, a lower alkoxy group, a nitro group, an amino group, or a carboxyl group.

  提供了一种新型洛索洛芬衍生物，该衍生物没有胃肠道障碍等副作用，同时具有优秀的抗炎和镇痛作用，其化学结构如下所示（式中R1和R2分别代表卤素原子或取代或未取代的苯基），或其药学上可接受的盐。在该衍生物中，卤素原子可选自氯原子、溴原子、氟原子和碘原子，取代苯基的取代基为卤素原子、羟基、取代或未取代的较低烷基基团、较低烷基硫基团、较低烷氧基团、硝基基团、氨基或羧基。
• Synthesis and biological evaluation of loxoprofen derivatives
  作者：Naoki Yamakawa、Shintaro Suemasu、Masaaki Matoyama、Ken-ichiro Tanaka、Takashi Katsu、Keishi Miyata、Yoshinari Okamoto、Masami Otsuka、Tohru Mizushima

  DOI：10.1016/j.bmc.2011.04.050

  日期：2011.6

  Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-4'-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID. (C) 2011 Elsevier Ltd. All rights reserved.
• Properties and Synthesis of 2-{2-Fluoro (or Bromo)-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic Acid: Nonsteroidal Anti-inflammatory Drugs with Low Membrane Permeabilizing and Gastric Lesion-Producing Activities
  作者：Naoki Yamakawa、Shintaro Suemasu、Masaaki Matoyama、Ayumi Kimoto、Miho Takeda、Ken-ichiro Tanaka、Tomoaki Ishihara、Takashi Katsu、Yoshinari Okamoto、Masami Otsuka、Tohru Mizushima

  DOI：10.1021/jm101116s

  日期：2010.11.11

  We previously proposed that membrane permeabilization activity of NSAIDs is involved in NSAID-induced gastric lesions. We here synthesized derivatives of loxoprofen that have lower membrane permeabilization activity than other NSAIDs. Compared to loxoprofen, the derivatives 10a and 10b have lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 10a and 10b are likely to be therapeutically beneficial as safer NSAIDs.