(+/-)-2-<4-(cis-2-hydroxycyclopentylmethyl)phenyl>propionic acid

• 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-<4-(cis-2-hydroxycyclopentylmethyl)phenyl>propionic acid
• 英文别名: (+/-)-2-[4-(cis)-((1'R,2'R)-2'-hydroxycyclopentylmethyl)-phenyl]propionic acid；2-(4-(((1,2-cis)-2-Hydroxycyclopentyl)methyl)phenyl)propanoic acid；2-[4-[[(1S,2S)-2-hydroxycyclopentyl]methyl]phenyl]propanoic acid
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: SHAHPWSYJFYMRX-RYQGGHCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-2-<4-(cis-2-hydroxycyclopentylmethyl)phenyl>propionic acid 在 双氧水 、 三氟乙酸 作用下， 反应 1.5h， 以50 mg的产率得到cis-hexahydro-2H-cyclopenta[b]furan-2-one
  参考文献：
  名称：

  Synthesis of the eight possible optically active isomers of 2-(4-(2-hydroxycyclopentylmethyl)phenyl)propionic acid.

  摘要：

  最近合成的一种化合物(±)-2-[4-(2-氧代环戊基甲基)苯基]丙酸具有良好的抗炎和镇痛活性。与母酸相比，该化合物的一种代谢物具有更强的前列腺素合成酶抑制活性。为了确定代谢物的结构和绝对构型分配，我们合成了 8 种可能的标题醇，并对这些醇进行了立体化学分配。

  DOI：

  10.1248/cpb.31.4319
• 作为产物：
  描述：

  洛索洛芬 在 potassium tri-sec-butyl-borohydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以197 mg的产率得到(+/-)-2-<4-(cis-2-hydroxycyclopentylmethyl)phenyl>propionic acid
  参考文献：
  名称：

  Synthesis of the eight possible optically active isomers of 2-(4-(2-hydroxycyclopentylmethyl)phenyl)propionic acid.

  摘要：

  最近合成的一种化合物(±)-2-[4-(2-氧代环戊基甲基)苯基]丙酸具有良好的抗炎和镇痛活性。与母酸相比，该化合物的一种代谢物具有更强的前列腺素合成酶抑制活性。为了确定代谢物的结构和绝对构型分配，我们合成了 8 种可能的标题醇，并对这些醇进行了立体化学分配。

  DOI：

  10.1248/cpb.31.4319

文献信息

• Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver
  作者：Hirotami Ohara、Yoshiyuki Miyabe、Yoshihiro Deyashiki、Kazuya Matsuura、Akira Kara

  DOI：10.1016/0006-2952(95)00124-i

  日期：1995.7

  In this study, we compared the enzymatic reduction of 10 drugs with a ketone group by homogeneous carbonyl reductase, aldehyde reductase and three dihydrodiol dehydrogenases of human liver cytosol. At least one and in some cases all of the three dihydrodiol dehydrogenases reduced each of the ten drugs. Among these naloxone, naltrexone, befunolol, ethacrynic acid and ketoprofen were substrates specific

  在这项研究中，我们比较了人肝细胞溶质的均相羰基还原酶，醛还原酶和三种二氢二醇脱氢酶对10种带有酮基的药物的酶促还原作用。三种二氢二醇脱氢酶中至少一种，在某些情况下，全部还原了十种药物。在这些纳洛酮中，纳曲酮，倍氟洛尔，乙炔酸和酮洛芬是脱氢酶特异的底物。羰基还原酶和/或醛还原酶大大降低了其他药物-氟哌啶醇，甲吡酮，洛索洛芬，柔红霉素和乙酰己酰胺的含量。二氢二醇脱氢酶还显示氟哌啶醇和洛索洛芬的Km值低于羰基还原酶的Km值。结果表明，三种二氢二醇脱氢酶以及两种还原酶，
• Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2
  作者：Denis Riendeau、Myriam Salem、Angela Styhler、Marc Ouellet、Joseph A Mancini、Chun Sing Li

  DOI：10.1016/j.bmcl.2003.12.047

  日期：2004.3

  Loxoprofen, its trans-alcohol and cis-alcohol metabolites were evaluated for selectivity of inhibition of COX-2 over COX-1. The (2S,1'R,2'S)-trans-alcohol derivative was found to be the most active metabolite and to be a potent and nonselective inhibitor of COX-2 and COX-1 in both enzyme and human whole blood assays. (C) 2004 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.
• US4599360A
  申请人：——

  公开号：US4599360A

  公开（公告）日：1986-07-08
• Synthesis of the eight possible optically active isomers of 2-(4-(2-hydroxycyclopentylmethyl)phenyl)propionic acid.
  作者：SHUNJI NARUTO、ATSUSUKE TERADA

  DOI：10.1248/cpb.31.4319

  日期：——

  A recently synthesized compound, (±)-2-[4-(2-oxocyclopentylmethyl) phenyl] propionic acid, had good anti-inflammatory and analgesic activities. One of the metabolites of this compound showed more potent prostaglandin synthetase inhibitory activity than the parent acid. For the structural determination and absolute configurational assignment of the metabolites, we synthesized the eight possible title alcohols and carried out stereochemical assignment of these alcohols.

  最近合成的一种化合物(±)-2-[4-(2-氧代环戊基甲基)苯基]丙酸具有良好的抗炎和镇痛活性。与母酸相比，该化合物的一种代谢物具有更强的前列腺素合成酶抑制活性。为了确定代谢物的结构和绝对构型分配，我们合成了 8 种可能的标题醇，并对这些醇进行了立体化学分配。