6,8-difluoro-4-oxo-4H-chromene-2-carboxylic acid | 915146-44-0

• 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: 6,8-difluoro-4-oxo-4H-chromene-2-carboxylic acid
• 英文别名: 6,8-Difluoro-4-oxochromene-2-carboxylic acid
• CAS: 915146-44-0
• 化学式: C₁₀H₄F₂O₄
• mdl: MFCD11868712
• 分子量: 226.136
• InChiKey: MIKPQSQDFXSSIY-UHFFFAOYSA-N

物化性质

• 沸点：
  348.1±42.0 °C(Predicted)
• 密度：
  1.665±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-amine dihydrochloride 、 6,8-difluoro-4-oxo-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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以25%的产率得到N-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]-7,8-difluoro-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：

  acetic acid 2,4-difluorophenyl ester 在 三氯化铝 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 33.0h， 生成 6,8-difluoro-4-oxo-4H-chromene-2-carboxylic acid
  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

文献信息

• [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。
• [EN] ANTI-INFECTIVE AGENTS<br/>[FR] AGENTS ANTI-INFECTIEUX
  申请人：UNIV DUNDEE

  公开号：WO2017221002A1

  公开（公告）日：2017-12-28

  The present invention relates to a novel class of chromene-2-carboxamide compounds inhibitors of general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined herein, to their use in medicine, and their use as anti-infective agents in particular, to compositions containing them, to processes for their preparation and to intermediates used in such processes.

  本发明涉及一类新型的基于色酮-2-羧酰胺化合物的抑制剂，其通式为(I)，其中R1、R2、R3、R4、R5、R6、R7、R8和X如本文所定义，其在医学上的用途，特别是作为抗感染剂的用途，包括含有它们的组合物，其制备过程以及用于这些过程的中间体。
• [EN] SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS<br/>[FR] DERIVES DE PIPERIDINE ET DE PIPERAZINE SUBSTITUES UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR DE LA MELANOCORTINE-4
  申请人：MYOCONTRACT LTD

  公开号：WO2004083208A1

  公开（公告）日：2004-09-30

  The present invention relates to novel substituted piperidine and piperazine derivatives as melanocortin-4 receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders, where the regulation of the MC-4R is involved, can be treated with the compounds of the invention.

  本发明涉及一种新型的替代哌啶和哌嗪衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明的MC-4R激动剂可用于治疗肥胖、糖尿病和性功能障碍等疾病，而MC-4R拮抗剂可用于治疗癌症恶病质、肌肉消耗、厌食症、焦虑和抑郁等疾病。所有涉及MC-4R调节的疾病和障碍均可使用本发明的化合物治疗。
• [EN] SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS<br/>[FR] DERIVES A SUBSTITUTION PIPERIDINE ET PIPERAZINE AGISSANT COMME MODULATEURS DU RECEPTEUR DE LA MELANOCORTINE 4
  申请人：MYOCONTRACT LTD

  公开号：WO2004083199A1

  公开（公告）日：2004-09-30

  The present invention relates to novel substituted piperidine and piperazine derivatives as melanocortin-4 receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes, and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders where the regulation of the MC-4R is involved can be treated with the compounds of the invention.

  本发明涉及一种新型的取代哌啶和哌嗪衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明中的MC-4R激动剂可用于治疗肥胖症、糖尿病和性功能障碍等疾病和疾病，而MC-4R拮抗剂则可用于治疗癌症恶病质、肌肉萎缩、厌食、焦虑和抑郁等疾病和疾病。所有涉及MC-4R调节的疾病和疾病都可以用本发明中的化合物进行治疗。
• Substituted cyclohexyl and piperidinyl derivates as melanocortin-4 receptor modulators
  申请人：Soeberdt Michael

  公开号：US20070155783A1

  公开（公告）日：2007-07-05

  The present invention relates to novel substituted cyclohexyl and piperidinyl derivatives as melanocortin-4. receptor (MC-4R) modulators. MC-4R agonists of the invention can be used for the treatment of disorders and diseases such as obesity, diabetes and sexual dysfunction, whereas the MC-4R antagonists are useful for the treatment of disorders and diseases such as cancer cachexia, muscle wasting, anorexia, anxiety and depression. All diseases and disorders where the regulation of the MC-4R is involved can be treated with the compounds of the invention.

  本发明涉及一种新型的取代环己基和哌啶基衍生物，作为黑色素皮质素-4受体（MC-4R）调节剂。本发明中的MC-4R激动剂可用于治疗肥胖症、糖尿病和性功能障碍等疾病和疾病，而MC-4R拮抗剂则可用于治疗癌症消瘦、肌肉消耗、厌食、焦虑和抑郁等疾病和疾病。所有涉及MC-4R调节的疾病和疾病均可使用本发明中的化合物进行治疗。