2-(4-(naphthalen-2-ylamido)phenyl)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-(naphthalen-2-ylamido)phenyl)acetic acid
• 英文别名: 2-[4-(Naphthalene-2-carbonylamino)phenyl]acetic acid
• 化学式: C₁₉H₁₅NO₃
• 分子量: 305.333
• InChiKey: JAXLYFMPMURDJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二氧化碳-13C 、 2-(4-(naphthalen-2-ylamido)phenyl)acetic acid 在 caesium carbonate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 3.0h， 以8.5 mg的产率得到[¹³C]2-[4-(naphthalene-2-carbonylamino)phenyl]acetic acid
  参考文献：
  名称：

  苯乙酸的无过渡金属碳同位素交换。

  摘要：

  描述了在苯乙酸上无过渡金属的碳同位素交换程序。利用通用前驱体CO 2，该方案允许将碳同位素插入到羧酸位置，而无需前驱体合成。该程序可以标记15种药物，并且与碳同位素[ 14 C]和[ 13 C]兼容。还获得了具有低摩尔活性的[ 11 C]概念证明，对分布研究有价值。

  DOI：

  10.1002/anie.202002341
• 作为产物：
  描述：

  对氨基苯乙酸 、 2-萘甲酰氯 在 吡啶 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以73%的产率得到2-(4-(naphthalen-2-ylamido)phenyl)acetic acid
  参考文献：
  名称：

  Structural optimization and in vitro profiling of N-phenylbenzamide-based farnesoid X receptor antagonists

  摘要：

  Activation of the nuclear farnesoid X receptor (FXR) which acts as cellular bile acid sensor has been validated as therapeutic strategy to counter liver disorders such as non-alcoholic steatohepatitis by the clinical efficacy of obeticholic acid. FXR antagonism, in contrast, is less well studied and potent small molecule FXR antagonists are rare. Here we report the systematic optimization of a novel class of FXR antagonists towards low nanomolar potency. The most optimized compound antagonizes baseline and agonist induced FXR activity in a full length FXR reporter gene assay and represses intrinsic expression of FXR regulated genes in hepatoma cells. With this activity and a favorable toxicity-, stability- and selectivity-profile it appears suitable to further study FXR antagonism in vitro and in vivo.

  DOI：

  10.1016/j.bmc.2018.07.017

文献信息

• [EN] MODIFIED PENTAPEPTIDE ANTAGONISTS OF THE ATRIAL NATRIURETIC PEPTIDE CLEARANCE RECEPTOR<br/>[FR] ANTAGONISTES DE PENTAPEPTIDES MODIFIES DU RECEPTEUR DE LA CLAIRANCE DES PEPTIDES NATRIURETIQUES AURICULAIRES
  申请人：ASTRAZENECA AB

  公开号：WO2000061631A1

  公开（公告）日：2000-10-19

  A compound having general formula (A) and methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.
• Structural optimization and in vitro profiling of N-phenylbenzamide-based farnesoid X receptor antagonists
  作者：Jurema Schmidt、Simone Schierle、Leonie Gellrich、Astrid Kaiser、Daniel Merk

  DOI：10.1016/j.bmc.2018.07.017

  日期：2018.8

  Activation of the nuclear farnesoid X receptor (FXR) which acts as cellular bile acid sensor has been validated as therapeutic strategy to counter liver disorders such as non-alcoholic steatohepatitis by the clinical efficacy of obeticholic acid. FXR antagonism, in contrast, is less well studied and potent small molecule FXR antagonists are rare. Here we report the systematic optimization of a novel class of FXR antagonists towards low nanomolar potency. The most optimized compound antagonizes baseline and agonist induced FXR activity in a full length FXR reporter gene assay and represses intrinsic expression of FXR regulated genes in hepatoma cells. With this activity and a favorable toxicity-, stability- and selectivity-profile it appears suitable to further study FXR antagonism in vitro and in vivo.
• Transition‐Metal‐Free Carbon Isotope Exchange of Phenyl Acetic Acids
  作者：Gianluca Destro、Kaisa Horkka、Olivier Loreau、David‐Alexandre Buisson、Lee Kingston、Antonio Del Vecchio、Magnus Schou、Charles S. Elmore、Frédéric Taran、Thibault Cantat、Davide Audisio

  DOI：10.1002/anie.202002341

  日期：2020.8.3

  A transition‐metal‐free carbon isotope exchange procedure on phenyl acetic acids is described. Utilizing the universal precursor CO2, this protocol allows the carbon isotope to be inserted into the carboxylic acid position, with no need of precursor synthesis. This procedure enabled the labeling of 15 pharmaceuticals and was compatible with carbon isotopes [14C] and [13C]. A proof of concept with [11C]

  描述了在苯乙酸上无过渡金属的碳同位素交换程序。利用通用前驱体CO 2，该方案允许将碳同位素插入到羧酸位置，而无需前驱体合成。该程序可以标记15种药物，并且与碳同位素[ 14 C]和[ 13 C]兼容。还获得了具有低摩尔活性的[ 11 C]概念证明，对分布研究有价值。