5-chloro-2-(dibenzylphosphono)oxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide | 634913-38-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-chloro-2-(dibenzylphosphono)oxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide
• 英文别名: 5-chloro-2-(dibenzylphosphono)oxy-N-[3,5-di(trifluoromethyl)phenyl]benzoamide；Dibenzyl [2-[[3,5-bis(trifluoromethyl)phenyl]carbamoyl]-4-chlorophenyl] phosphate
• CAS: 634913-38-5
• 化学式: C₂₉H₂₁ClF₆NO₅P
• 分子量: 643.907
• InChiKey: AGIYUGPCVGTHPA-UHFFFAOYSA-N

物化性质

• 沸点：
  572.6±50.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-chloro-2-(dibenzylphosphono)oxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide 在 palladium hydroxide on carbon 氢气 、 sodium ethanolate 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 生成 2-((3,5-di(trifluoromethyl)phenyl)aminoformyl)-4-chlorophenyl hydrogen phosphate monosodium salt
  参考文献：
  名称：

  O-SUBSTITUTED HYDROXYARYL DERIVATIVES

  摘要：

  公开号：

  EP1512397B1
• 作为产物：
  描述：

  5-氯代水杨酸 在 四氯化碳 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 3.67h， 生成 5-chloro-2-(dibenzylphosphono)oxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  O-SUBSTITUTED HYDROXYARYL DERIVATIVES

  摘要：

  公开号：

  EP1512397B1

文献信息

• O-substituted hydroxyaryl derivatives
  申请人：Muto Susumu

  公开号：US20060094718A1

  公开（公告）日：2006-05-04

  A medicament having inhibitory activity against NF-κB activation which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in a main chain is 2 to 5 (said connecting group may be substituted), “A” represents an acyl group which may be substituted, (provided that unsubstituted acetyl group and unsubstituted acryloyl group are excluded,) or a C 1 to C 6 alkyl group which may be substituted, or A may bind to connecting group X to form a cyclic structure which may be substituted, “E” represents an aryl group which may be substituted or a heteroaryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above.

  一种药物具有抑制NF-κB激活活性，其包括以下通式(I)所表示的化合物或其药学上可接受的盐、水合物或溶剂化物作为活性成分，其中X表示主链中原子数为2至5的连接基（该连接基可以被取代），A表示可以被取代的酰基（不包括未取代的乙酰基和未取代的丙烯酰基）或者可以被取代的C1到C6烷基，或者A可以与连接基X结合形成可以被取代的环状结构，E表示可以被取代的芳基或者可以被取代的杂环基，环Z表示可以具有一个或多个取代基的芳基（除了由式—O-A所表示的基团外，A具有与上述定义相同的含义，由式—X-E所表示的基团，X和E具有与上述定义相同的含义）或者可以具有一个或多个取代基的杂环基（除了由式—O-A所表示的基团外，A具有与上述定义相同的含义，由式—X-E所表示的基团，X和E具有与上述定义相同的含义）。
• NOVEL PRODRUG SALTS
  申请人：AEROMICS, INC.

  公开号：US20160264604A1

  公开（公告）日：2016-09-15

  Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

  提供了选择性水通道抑制剂的新型前药盐，它们作为药物的使用方法，以及包含它们的制药组合物，以及用于它们的合成的新型过程和中间体。还提供了一种化合物的使用，用于预防、治疗和控制水通道介导的疾病。水通道抑制剂，例如AQP4和/或AQP2的抑制剂，在治疗或控制水平衡失调的疾病方面可能具有用途，例如水肿（特别是脑和脊髓水肿）、低钠血症和多余液体潴留，以及癫痫、视网膜缺血和其他眼部疾病、心肌缺血、心肌缺血/再灌注损伤、心肌梗塞、心肌缺氧、充血性心力衰竭、败血症和神经肌病性视神经脊髓炎，以及偏头痛。
• Prodrug salts
  申请人：AEROMICS, INC.

  公开号：US10258636B2

  公开（公告）日：2019-04-16

  Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.

  本研究提供了选择性水蒸发蛋白抑制剂的新型原药盐、它们作为药物的用途、包含它们的药物组合物、合成它们的新型工艺以及用于合成它们的新型中间体。还提供了一种化合物在预防、治疗和控制水蒸发素介导的疾病方面的用途。水蒸发蛋白抑制剂，例如AQP4和/或AQP2的抑制剂，可用于治疗或控制水失衡疾病，例如水肿（尤其是脑和脊髓水肿）、低钠血症和过量液体潴留，以及癫痫等疾病、视网膜缺血和其他眼部疾病、心肌缺血、心肌缺血/再灌注损伤、心肌梗塞、心肌缺氧、充血性心力衰竭、败血症、神经脊髓炎以及偏头痛。
• Methods of treating cardiac edema, neuromyelitis optica, and hyponatremia
  申请人：Aeromics, Inc.

  公开号：US11084778B2

  公开（公告）日：2021-08-10

  The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.

  本发明涉及选择性水蒸发蛋白抑制剂（如水蒸发蛋白-4 或水蒸发蛋白-2）（如某些苯基苯甲酰胺化合物）在预防、治疗和控制水蒸发蛋白介导的疾病（如水失衡疾病）方面的用途，例如水肿（尤其是脑和脊髓水肿，如创伤或缺血性中风后的水肿，以及与胶质瘤、脑膜炎、急性登山病、癫痫发作、感染、代谢紊乱、低氧、缺血性脑卒中、颅内压增高、颅内压增高相关的水肿）、外伤或缺血性中风后的水肿，以及与胶质瘤、脑膜炎、急性高山病、癫痫发作、感染、代谢紊乱、缺氧、水中毒、肝功能衰竭、肝性脑病有关的水肿、糖尿病酮症酸中毒、脓肿、子痫、克雅氏病和狼疮性脑炎，以及微重力和/或辐射照射引起的水肿，以及侵入性中枢神经系统手术（如：手术）引起的水肿。g.,神经外科手术、血管内血块清除术、脊髓穿刺术、动脉瘤修补术或脑深部刺激术，以及视网膜水肿），以及低钠血症和体液潴留过多，以及癫痫、视网膜缺血等疾病和其他与眼内压和/或组织水合异常有关的眼部疾病、心肌缺血、心肌缺血/再灌注损伤、心肌梗塞、心肌缺氧、充血性心力衰竭、败血症和神经性视网膜炎以及偏头痛等疾病，以及用于鉴定水通道蛋白抑制剂的新型检测方法。
• Methods
  申请人：Aeromics, LLC

  公开号：US20150133405A1

  公开（公告）日：2015-05-14

  The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord, e.g., following trauma or ischemic stroke, as well as the edema associated with glioma, meningitis, acute mountain sickness, epileptic seizures, infections, metabolic disorders, hypoxia, water intoxication, hepatic failure, hepatic encephalopathy, diabetic ketoacidosis, abscess, eclampsia, Creutzfeldt-Jakob disease, and lupus cerebritis, as well as edema consequent to microgravity and/or radiation exposure, as well as edema consequent to invasive central nervous system procedures, e.g., neurosurgery, endovascular clot removal, spinal tap, aneurysm repair, or deep brain stimulation, as well as retinal edema), as well as hyponatremia and excess fluid retention, and diseases such as epilepsy, retinal ischemia and other diseases of the eye associated with abnormalities in intraocular pressure and/or tissue hydration, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines, as well as to novel assays for identifying aquaporin inhibitors.