3-氟-4-碘苯乙酸 | 1261874-58-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氟-4-碘苯乙酸
• 英文名称: 2-(3-Fluoro-4-iodophenyl)acetic acid
• CAS: 1261874-58-1
• 化学式: C₈H₆FIO₂
• 分子量: 280.037
• InChiKey: CMRUORQQYMIYDF-UHFFFAOYSA-N

物化性质

• 沸点：
  319.6±27.0 °C(Predicted)
• 密度：
  1.956±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-氟-4-碘苯乙酸 在 硫酸 、 palladium diacetate 、 potassium carbonate 作用下， 以 乙二醇甲醚 、 水 为溶剂， 反应 30.0h， 生成 methyl 2-[3-fluoro-4-(3-hydroxyphenyl)phenyl]acetate
  参考文献：
  名称：

  Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies

  摘要：

  Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.036

文献信息

• A one-pot Pd- and P450-catalyzed chemoenzymatic synthesis of a library of oxyfunctionalized biaryl alkanoic acids leveraging a substrate anchoring approach
  作者：Mallory Kato、Michael Huynh、Nicholas Chan、Julien Elliott、Amie Trinh、Kathreena Lucero、Julia Vu、Daniel Parker、Lionel E. Cheruzel

  DOI：10.1016/j.jinorgbio.2023.112240

  日期：2023.8

  position. Moreover, in order to increase the biocatalytic product conversion, a reversible substrate engineering approach was developed. This involves the coupling of a bulky amino acid such as L- phenylalanine or tryptophan, to the carboxylic acid moiety. The approach resulted in a 14 to 49% overall biocatalytic product conversion increase associated with a change in regioselectivity of hydroxylation

  通过将钯催化与选择性细胞色素 P450 酶氧功能化相结合，开发了一种一锅化学酶法。各种碘苯基链烷酸可以与烷基苯基硼酸偶联，以总体高产率生成一系列烷基取代的联芳基链烷酸。产品的身份可以通过各种分析和色谱技术来确认。化学反应完成后，添加具有过氧化酶活性的工程化细胞色素 P450 血红素结构域突变体，导致这些化合物选择性氧官能化，主要是在苄基位置。此外，为了提高生物催化产物转化率，开发了可逆底物工程方法。这涉及将大体积氨基酸（例如L-苯丙氨酸或色氨酸）与羧酸部分偶联。该方法使总体生物催化产物转化率提高了 14% 至 49%，这与羟基化区域选择性向不太有利的位置的变化有关。
• HYDROXY CONTAINING FXR (NR1H4) MODULATING COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：EP3233850B1

  公开（公告）日：2019-04-03
• Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies
  作者：Marco Migliore、Damien Habrant、Oscar Sasso、Clara Albani、Sine Mandrup Bertozzi、Andrea Armirotti、Daniele Piomelli、Rita Scarpelli

  DOI：10.1016/j.ejmech.2015.12.036

  日期：2016.2

  Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.