4-oxo-6-(trifluoromethyl)-4H-chromene-2-carboxylic acid | 638192-27-5

• 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-6-(trifluoromethyl)-4H-chromene-2-carboxylic acid
• 英文别名: 4-Oxo-6-trifluoromethyl-4h-chromene-2-carboxylic acid；4-oxo-6-(trifluoromethyl)chromene-2-carboxylic acid
• CAS: 638192-27-5
• 化学式: C₁₁H₅F₃O₄
• 分子量: 258.154
• InChiKey: QGZMUTNXHHFLFE-UHFFFAOYSA-N

物化性质

• 沸点：
  343.9±42.0 °C(Predicted)
• 密度：
  1.604±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

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-6-(trifluoromethyl)-4H-chromene-2-carboxylic acid 生成 4-chloro-6-trifluoromethyl-chromen-2-one
  参考文献：
  名称：

  [EN] ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR
  [FR] ANTAGONISTES DU RECEPTEUR DE L'HORMONE DE MELANO-CONCENTRATION

  摘要：

  公开号：

  WO2003106452A3
• 作为产物：
  描述：

  对三氟甲基苯酚 在 甲烷磺酸 、 phosphorus pentoxide 、 苄基三甲基氢氧化铵 作用下， 以 1,4-二氧六环 为溶剂， 反应 21.5h， 生成 4-oxo-6-(trifluoromethyl)-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 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] MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] MODULATEURS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2022094244A1

  公开（公告）日：2022-05-05

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

  本文提供了一些化合物、组合物和方法，用于调节综合应激反应（ISR）和治疗相关疾病、疾患和病况。
• [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。
• Antagonists of melanin concentrating hormone receptor
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040106645A1

  公开（公告）日：2004-06-03

  This invention provides compounds that are antagonists of melanin concentrating hormone receptor-1 (MCH-R1). The compounds are represented by formula I: 1 where m is zero or one, n is zero to two, Y is oxygen or —N(R 9 )—, R 1 , R 2 , R 3 , R 4 , R 5 , R 9 and Ring A are defined in the specification. Coumarin and quinolone compounds where R 1 and R 2 together form a fused benzo ring are preferred. The invention also provides compounds of formula VI where the coumarin moiety is replaced by a quinazolinone ring. The compounds are useful for treating MCH-R1-related disorders, particularly overweight conditions including obesity.

  这项发明提供了一些与黑色素浓集激素受体-1 (MCH-R1) 相对抗的化合物。这些化合物由公式 I 表示：其中 m 为零或一，n 为零至二，Y 为氧或 —N(R9)—，R1、R2、R3、R4、R5、R9 和环 A 在说明书中有定义。偏好使用 R1 和 R2 结合形成融合苯环的香豆素和喹啉类化合物。该发明还提供了公式 VI 的化合物，其中香豆素基团被喹嗪酮环替换。这些化合物可用于治疗与 MCH-R1 相关的疾病，特别是超重症，包括肥胖症。
• 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。