4-oxo-7-(trifluoromethyl)-4H-chromene-2-carboxylic acid | 915146-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-oxo-7-(trifluoromethyl)-4H-chromene-2-carboxylic acid
• 英文别名: 4-oxo-7-(trifluoromethyl)chromene-2-carboxylic acid
• CAS: 915146-41-7
• 化学式: C₁₁H₅F₃O₄
• 分子量: 258.154
• InChiKey: LRGUFKIEONODTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-oxo-7-(trifluoromethyl)-4H-chromene-2-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 (piperidin-4-yl)-7-trifluoromethyl-4-oxo-4H-chromene-2-carboxamide
  参考文献：
  名称：

  Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety

  摘要：

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.

  DOI：

  10.1021/jm060683e
• 作为产物：
  描述：

  1-[2-羟基-4-(三氟甲基)苯基]乙酮 在 盐酸 、 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 4-oxo-7-(trifluoromethyl)-4H-chromene-2-carboxylic acid
  参考文献：
  名称：

  [EN] SUBSTITUTED CYCLOLAKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY
  [FR] CYCLOLALKYLES SUBSTITUÉS EN TANT QUE MODULATEURS DE LA VOIE DE STRESS INTÉGRÉE

  摘要：

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾病和症状的化合物、组合物和方法。

  公开号：

  WO2020223536A1

文献信息

• MODULATORS OF THE INTEGRATED STRESS PATHWAY
  申请人：Calico Life Sciences LLC

  公开号：US20210363136A1

  公开（公告）日：2021-11-25

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.
• Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety
  作者：John K. Lynch、Jennifer C. Freeman、Andrew S. Judd、Rajesh Iyengar、Mathew Mulhern、Gang Zhao、James J. Napier、Dariusz Wodka、Sevan Brodjian、Brian D. Dayton、Doug Falls、Christopher Ogiela、Regina M. Reilly、Thomas J. Campbell、James S. Polakowski、Lisa Hernandez、Kennan C. Marsh、Robin Shapiro、Victoria Knourek-Segel、Brian Droz、Eugene Bush、Michael Brune、Lee C. Preusser、Ryan M. Fryer、Glenn A. Reinhart、Kathryn Houseman、Gilbert Diaz、Ann Mikhail、James T. Limberis、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1021/jm060683e

  日期：2006.11.1

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.
• [EN] SUBSTITUTED CYCLOLAKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] CYCLOLALKYLES SUBSTITUÉS EN TANT QUE MODULATEURS DE LA VOIE DE STRESS INTÉGRÉE
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2020223536A1

  公开（公告）日：2020-11-05

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾病和症状的化合物、组合物和方法。