(E)-3-[3,4-bis(difluoromethoxy)phenyl]-2-propenoic acid | 1164145-18-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-[3,4-bis(difluoromethoxy)phenyl]-2-propenoic acid
• 英文别名: (E)-3,4-bis(difluoromethoxy)phenyl-2-propenoic acid；2-Propenoic acid, 3-[3,4-bis(difluoromethoxy)phenyl]-, (2E)-；(E)-3-[3,4-bis(difluoromethoxy)phenyl]prop-2-enoic acid
• CAS: 1164145-18-9
• 化学式: C₁₁H₈F₄O₄
• 分子量: 280.176
• InChiKey: FWWPYJOEBWHNMW-DUXPYHPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (E)-3-[3,4-bis(difluoromethoxy)phenyl]-2-propenoic acid 在 草酰氯 、 硫酸 、 palladium diacetate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 2-(3,4-bis(difluoromethoxy)phenyl)cyclopropanecarboxylic acid chloride
  参考文献：
  名称：

  3′,4′-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy

  摘要：

  Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-beta-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 mu M). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), C-max of 200 mu M and T-max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.100
• 作为产物：
  描述：

  3,4-二羟基苯甲醛 在 哌啶 、 吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 (E)-3-[3,4-bis(difluoromethoxy)phenyl]-2-propenoic acid
  参考文献：
  名称：

  3′,4′-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy

  摘要：

  Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-beta-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 mu M). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), C-max of 200 mu M and T-max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.100

文献信息

• [EN] HALOGENATED ANALOGUES OF ANTI-FIBROTIC AGENTS<br/>[FR] ANALOGUES HALOGÉNÉS D'AGENTS ANTIFIBROTIQUES
  申请人：FIBROTECH THERAPEUTICS PTY LTD

  公开号：WO2009079692A1

  公开（公告）日：2009-07-02

  The present invention relates to halogenated compounds of formula (I) with the substituents as described within the specification. The compounds may be useful as anti-fibrqtic agents. The present invention also relates to methods for their preparation.

  本发明涉及具有规定的取代基的式(I)的卤代化合物。这些化合物可能作为抗纤维化剂有用。本发明还涉及它们的制备方法。
• [EN] PURINE COMPOUNDS FOR TREATING DISORDERS<br/>[FR] COMPOSÉS DE PURINE POUR TRAITER DES TROUBLES
  申请人：MARVEL BIOTECHNOLOGY

  公开号：WO2021179074A1

  公开（公告）日：2021-09-16

  Substituted purine compounds of formula (I)-(III) and salts thereof act as adenosine A2a receptor (A2aR) antagonists for cancer immunotherapy, depression, anxiety, multiple sclerosis, NASH, scleroderma, ADHD, Alzheimer's 5 and Parkinsons. Pharmaceutical compositions comprising such compounds, and methods of their use in treating depression are also taught.

  公式（I）-（III）的嘌呤化合物及其盐作为腺苷A2a受体（A2aR）拮抗剂，用于癌症免疫疗法、抑郁症、焦虑症、多发性硬化症、NASH、硬皮病、ADHD、阿尔茨海默病和帕金森病。包含这种化合物的药物组合物，以及在治疗抑郁症中使用它们的方法也得到了教导。
• HALOGENATED ANALOGUES OF ANTI-FIBROTIC AGENTS
  申请人：Kelly Darren James

  公开号：US20120059188A9

  公开（公告）日：2012-03-08

  The present invention relates to halogenated compounds of formula (I) with the substituents as described within the specification. The compounds may be useful as anti-fibrotic agents. The present invention also relates to methods for their preparation.

  本发明涉及式(I)的卤代化合物，所述化合物的取代基如规范中所述。该化合物可以用作抗纤维化剂。本发明还涉及其制备方法。
• US8624056B2
  申请人：——

  公开号：US8624056B2

  公开（公告）日：2014-01-07
• 3′,4′-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy
  作者：Spencer J. Williams、Steven C. Zammit、Alison J. Cox、David M. Shackleford、Julia Morizzi、Yuan Zhang、Andrew K. Powell、Richard E. Gilbert、Henry Krum、Darren J. Kelly

  DOI：10.1016/j.bmcl.2013.09.100

  日期：2013.12

  Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-beta-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 mu M). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), C-max of 200 mu M and T-max of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy. (C) 2013 Elsevier Ltd. All rights reserved.