5-chloro-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxybenzamide

• 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-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxybenzamide
• 英文别名: 5-Chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-hydroxybenzamide
• 化学式: C₁₄H₈ClF₄NO₂
• 分子量: 333.67
• InChiKey: XOJZVNXJYRVDTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 、 4-氟-3-三氟甲基苯胺 在 吡啶 、 三氯化磷 作用下， 以 甲苯 为溶剂， 反应 12.0h， 生成 5-chloro-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxybenzamide
  参考文献：
  名称：

  Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling

  摘要：

  A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.10.056

文献信息

• 2-HYDROXYARYLAMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Korea Research Institute of Bioscience and Biotechnology

  公开号：US20140221411A1

  公开（公告）日：2014-08-07

  The present invention relates to a 2-hydroxyarylamide derivative or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. The 2-hydroxyarylamide derivative prepared by the present invention is excellent in the inhibition of the activity of TMPRSS4 serine protease and the suppression of the infiltration of TMPRSS4-expressed cancer cells, and thus can be useful as a composition for preventing or treating cancer by inhibiting TMPRSS4 over-expressed in cancer cells, particularly, colorectal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, or stomach cancer cells.

  本发明涉及一种2-羟基芳酰胺衍生物或其药用可接受的盐，其制备方法，以及作为活性成分的预防或治疗癌症的药物组合物。本发明制备的2-羟基芳酰胺衍生物在抑制TMPRSS4丝氨酸蛋白酶的活性和抑制TMPRSS4表达的癌细胞浸润方面表现出色，因此可以作为一种通过抑制癌细胞中TMPRSS4过度表达的组合物，特别是结肠癌、肺癌、乳腺癌、前列腺癌、卵巢癌、胰腺癌或胃癌细胞的预防或治疗癌症的组合物。
• INFLAMMATORY CYTOKINE RELEASE INHIBITOR
  申请人：MUTO Susumu

  公开号：US20090192122A2

  公开（公告）日：2009-07-30

  A medicament having inhibitory activity against NF-κB activation, which comprises a compound represented by the following general formula (I) or a pharmacologically acceptable salt as an active ingredient: wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.

  一种具有抑制NF-κB激活活性的药物，其包括以下通式(I)所表示的化合物或其药理学上可接受的盐作为活性成分：其中X代表连接基，A代表氢原子或乙酰基，E代表芳基或杂芳基，环X代表芳烃或杂芳烃。
• Inhibitors against the production and release of inflammatory cytokines
  申请人：——

  公开号：US20040259877A1

  公开（公告）日：2004-12-23

  A medicament having inhibitory activity against NF-&kgr;B activation, which comprises a compound represented by the following general formula (I) or a pharmacologically acceptable salt as an active ingredient: 1 wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.

  一种具有抑制NF-&kgr;B激活活性的药物，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作为活性成分：1其中X表示连接基，A表示氢原子或乙酰基，E表示芳基或杂芳基，环X表示芳烃或杂芳烃。
• Inflammatory cytokine release inhibitor
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：US08097759B2

  公开（公告）日：2012-01-17

  A medicament having inhibitory activity against NF-κB activation, which comprises a compound represented by the following general formula (I) or a pharmacologically acceptable salt as an active ingredient: wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.

  一种具有抑制NF-κB活化活性的药物，其包括以下一般公式(I)所代表的化合物或药理学上可接受的盐作为活性成分：其中X代表连接基，A代表氢原子或乙酰基，E代表芳基或杂芳基，环X代表芳烃或杂芳烃。
• 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。