5-fluoro-2-(4-fluorophenyl)benzo[d]isothiazol-3(2H)-one | 1186650-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 5-fluoro-2-(4-fluorophenyl)benzo[d]isothiazol-3(2H)-one
• 英文别名: 5-fluoro-2-(4-fluorophenyl)-2-hydrobenzo[d]isothiazol-3-one；5-Fluoro-2-(4-fluorophenyl)-1,2-benzothiazol-3-one
• CAS: 1186650-22-5
• 化学式: C₁₃H₇F₂NOS
• 分子量: 263.267
• InChiKey: XWKLATXUASFJEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 二氯甲烷 为溶剂， 生成 5-fluoro-2-(4-fluorophenyl)benzo[d]isothiazol-3(2H)-one
  参考文献：
  名称：

  Potent, Selective, and Orally Available Benzoisothiazolone Phosphomannose Isomerase Inhibitors as Probes for Congenital Disorder of Glycosylation Ia

  摘要：

  We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PM), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes with phosphomannomutase 2 (PMM2) for Man-6-P, diverting this substrate from critical protein glycosylation events. In congenital disorder of glycosylation type Ia, PMM2 activity is compromised.; thus, PMI inhibition is a potential strategy for the development of therapeutics. High-throughput screening (HTS) and subsequent chemical optimization led to the identification of a novel class of benzoisothiazolones as potent PMI inhibitors having little or no PMM2 inhibition. Two complementary synthetic routes were developed, enabling the critical structural requirements for activity to be determined, and the compounds were subsequently profiled in biochemical and cellular assays to assess efficacy. The most promising compounds were also profiled for bioavailability parameters, including metabolic stability, plasma stability, and permeability. The pharmacokinetic profile of a representative of this series (compound 19; ML089) was also assessed, demonstrating the potential of this series for in vivo efficacy when dosed orally in disease models.

  DOI：

  10.1021/jm101401a

文献信息

• Peptidomimetics for the treatment of coronavirus and picornavirus infections
  申请人：Emory University

  公开号：US11207370B2

  公开（公告）日：2021-12-28

  Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

  用于预防、治疗或治愈人类或其他动物宿主冠状病毒、皮卡病毒和/或肝病毒科病毒感染的化合物、组合物和方法。可治疗的特定病毒包括肠道病毒。在一个实施方案中，化合物可用于治疗严重急性呼吸系统综合征病毒感染，如人冠状病毒 229E、SARS、MERS、SARS-CoV-1（OC43）和 SARS-CoV-2。在另一个实施方案中，这些方法用于治疗合并感染两种或两种以上这些病毒的患者，或合并感染一种或多种这些病毒和诺如病毒的患者。
• COMBINED MODALITIES FOR NUCLEOSIDES AND/OR NADPH OXIDASE (NOX) INHIBITORS AS MYELOID-SPECIFIC ANTIVIRAL AGENTS
  申请人：Emory University

  公开号：EP3732180A1

  公开（公告）日：2020-11-04
• BENZOISOTHIAZOLONES AS INHIBITORS OF PHOSPHOMANNOSE ISOMERASE
  申请人：Cosford Nicholas D. P.

  公开号：US20110257233A1

  公开（公告）日：2011-10-20

  The disclosure provides new compounds and compositions thereof, and methods for treating or ameliorating a disorder relating to CDG-Ia. In particular, the disclosure provides benzoisothiazolone inhibitors of PMI, which have been synthesized and their ability to drive glycosylation has been demonstrated. The disclosure provides two synthetic routes for these compounds, including a new copper-catalyzed N-arylation reaction amenable to parallel derivitization. The disclosed compounds represent potent inhibitors of PMI, and their dose-dependent efficacy in cell-based models of glycosylation have been demonstrated. In addition, the disclosed compounds are selective over PMM and therefore, are useful in treating or ameliorating a disorder relating to CDG-Ia.
• PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS
  申请人：Emory University

  公开号：US20210008150A1

  公开（公告）日：2021-01-14

  Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.
• [EN] INHIBITORS OF NOX ENZYMES AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'ENZYMES NOX ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV EMORY

  公开号：WO2011062864A2

  公开（公告）日：2011-05-26

  Inhibitors of Nox enzymes, such as Noxl, Nox2, and Nox3, and methods of making and using such compounds are describe herein.