N-(3-叔丁基苯基)-5-氯-2-羟基苯甲酰胺 | 634186-63-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(3-叔丁基苯基)-5-氯-2-羟基苯甲酰胺
• 英文名称: N-(3-tert-butylphenyl)-5-chloro-2-hydroxybenzamide
• CAS: 634186-63-3
• 化学式: C₁₇H₁₈ClNO₂
• 分子量: 303.788
• InChiKey: APRLJIKXNXQBNL-UHFFFAOYSA-N

物化性质

• 沸点：
  375.6±42.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(3-叔丁基苯基)-5-氯-2-羟基苯甲酰胺
  参考文献：
  名称：

  针对 SARS-CoV-2 的氯硝柳胺类似物的设计、合成和生物学评价

  摘要：

  氯硝柳胺是一种广泛使用的驱虫药，通过TMEM16F抑制和自噬诱导复制来抑制SARS-CoV-2病毒进入，但相对较高的细胞毒性和较差的口服生物利用度限制了其应用。我们合成了 22 种氯硝柳胺类似物，其中发现化合物5具有最佳的抗 SARS-CoV-2 功效（IC 50  = 0.057 μM)和化合物6、10和11（IC 50 = 0.39、0.38 和 0.49 μM，分别）显示出与氯硝柳胺相当的功效。另一方面，化合物5、6、11在人血浆和肝脏S9酶测定中比氯硝柳胺具有更高的稳定性，口服给药时可以提高生物利用度和半衰期。荧光显微镜显示，与氯硝柳胺相比，化合物5在减少磷脂酰丝氨酸外化方面表现出更好的活性，这与 TMEM16F 抑制有关。应用人工智能预测的人TMEM16F蛋白结构进行分子对接，揭示5的4′-NO 2与Arg809形成氢键，而氯硝柳胺则被2′-Cl阻断。

  DOI：

  10.1016/j.ejmech.2022.114295

文献信息

• Method of use of pharmaceutical formulations for the treatment of apicomplexan diseases in animals
  申请人：Wood Richard Delarey

  公开号：US20130324555A1

  公开（公告）日：2013-12-05

  The present invention is directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a salicylanilide or salicylanilide derivative, disclosed herein, alone or in combination with one or more other active or excipient pharmaceutical substances. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein, further comprised of one or more active or excipient pharmaceutical substances.

  本发明涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物单独或与一个或多个其他活性或赋形剂药物物质结合而成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成，进一步包括一个或多个活性或赋形剂药物物质。
• Glutamate receptor modulators and therapeutic agents
  申请人：Wood Richard Delarey

  公开号：US20090239919A1

  公开（公告）日：2009-09-24

  The present invention discloses methods of modulating the activity of Group I mGluRs using a defined class of benzamide compounds. In one embodiment, methods of modulating the activity of mGluR1 are provided. In another embodiment, methods of modulating the activity of mGluR5 are provided. In still another embodiment, methods of simultaneously modulating the activities of both mGluR1 and mGluR5 are provided. The present invention also provides methods of treating diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of benzamide compounds. The present invention further provides methods of preventing diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of compounds. Diseases and disorders contemplated include, inter alia, diseases and disorders of the central nervous system, the peripheral nervous system, the gastrointestinal system, the circulatory system, skin, retina, brain, heart, and lungs.

  本发明公开了利用一类明确定义的苯甲酰胺化合物调节I类mGluRs活性的方法。在一个实施例中，提供了调节mGluR1活性的方法。在另一个实施例中，提供了调节mGluR5活性的方法。在另一个实施例中，提供了同时调节mGluR1和mGluR5活性的方法。本发明还提供了利用属于明确定定义的苯甲酰胺化合物类的一个或多个化合物治疗由I类mGluRs完全或部分介导的疾病或紊乱的方法。本发明还提供了利用属于明确定定义的化合物类的一个或多个化合物预防由I类mGluRs完全或部分介导的疾病或紊乱的方法。所考虑的疾病和紊乱包括中枢神经系统、外周神经系统、胃肠系统、循环系统、皮肤、视网膜、大脑、心脏和肺等疾病和紊乱。
• Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists
  作者：Maoqun Tian、Aliaa Abdelrahman、Younis Baqi、Eduardo Fuentes、Djamil Azazna、Claudia Spanier、Sabrina Densborn、Sonja Hinz、Ralf Schmid、Christa E. Müller

  DOI：10.1021/acs.jmedchem.0c00435

  日期：2020.6.11

  Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (1, IC50 0.0192 mu M) and N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide (14, IC50 0.0231 mu M), displayed >500-fold selectivity versus P2X2 and P2X3, and 10-fold selectivity versus P2X4 and P2X7 receptors, and inhibited collagen-induced platelet aggregation. They behaved as negative allosteric modulators, and molecular modeling studies suggested an extracellular binding site. Besides selective P2X1 antagonists, compounds with ancillary P2X4 and/or P2X7 receptor inhibition were discovered. These compounds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.
• Salicylanilide Inhibitors of Toxoplasma gondii
  作者：Alina Fomovska、Richard D. Wood、Ernest Mui、Jitenter P. Dubey、Leandra R. Ferreira、Mark R. Hickman、Patricia J. Lee、Susan E. Leed、Jennifer M. Auschwitz、William J. Welsh、Caroline Sommerville、Stuart Woods、Craig Roberts、Rima McLeod

  DOI：10.1021/jm3007596

  日期：2012.10.11

  Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose antiapicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles.
• US8211882B2
  申请人：——

  公开号：US8211882B2

  公开（公告）日：2012-07-03