2-[3-(trifluoromethyl)phenyl]benzo[d]isothiazol-3(2H)-one | 78471-91-7

• 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: 2-[3-(trifluoromethyl)phenyl]benzo[d]isothiazol-3(2H)-one
• 英文别名: 2-(3-trifluoromethylphenyl)-2-hydrobenzo[d]isothiazol-3-one；2-[3-(Trifluoromethyl)phenyl]-1,2-benzothiazol-3-one
• CAS: 78471-91-7
• 化学式: C₁₄H₈F₃NOS
• 分子量: 295.285
• InChiKey: ROHBTCZGZVBWBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  22.0
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2,2-二硫二苯甲酰氯 在 溴 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 2-[3-(trifluoromethyl)phenyl]benzo[d]isothiazol-3(2H)-one
  参考文献：
  名称：

  苯并异噻唑酮的广谱抗感染特性及其类似物的抗菌和抗真菌作用

  摘要：

  合成了各种单-和双-苯并噻吩并唑酮衍生物，并针对不同的细菌和真菌菌株进行了筛选，以了解多个亲电硫原子和活性硫紧邻区域的取代方式的影响。金黄色葡萄球菌-ATCC 7000699，MRSA和金黄色葡萄球菌-ATCC 29213（质量控制菌株）对此类化合物更敏感，而最有效的衍生物1.15的MIC 500.4μg/ mL（参见庆大霉素= 0.78μg/ mL）。CLogP值最好在2.5-3.5的范围内，它似乎对活性的贡献大于在氮上连接的基团的空间和电子效应。大体上，它们的抗真菌活性在结构和CLogP值方面也遵循相似的趋势。 N-苄基衍生物（1.7）对烟曲霉的最佳IC 50 = 0.1μg/ mL ; 它也是对强效的白色念珠菌，新型隐球菌，申克孢子丝，和近平滑念珠菌带IC 50值范围从0.4到1.3μg/ mL。初步研究还表明，这类化合物具有以低微摩尔范围的IC 50值靶向疟原虫的能力，并且可以通过结构优化来提高选择性。

  DOI：

  10.1016/j.bmcl.2017.01.027

文献信息

• [EN] METHODS AND COMPOUNDS TO TREAT SARS INFECTIONS<br/>[FR] PROCÉDÉS ET COMPOSÉS POUR TRAITER LES INFECTIONS À SARS-COV-2
  申请人：UNIV CALIFORNIA

  公开号：WO2022081984A1

  公开（公告）日：2022-04-21

  This disclosure features chemical entities (e.g., a compound (e.g., a compound of Formula (I), (II), (III), or (IV)), or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit the main protease (MPro) of a coronavirus (e.g., SARS-CoV-2). Said chemical entities are useful, e.g., for treating a coronavirus infection (e.g., SARS-CoV-2 infection (e.g., COVID-19)) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

  本文披露了一些化合物（例如，化合物（例如，公式（I），（II），（III）或（IV）的化合物），或药物的可接受盐，和/或水合物，和/或共晶体，和/或化合物的药物组合），它们能够抑制冠状病毒（例如，SARS-CoV-2）的主要蛋白酶（MPro）。这些化合物可用于治疗受体（例如，人类）的冠状病毒感染（例如，SARS-CoV-2感染（例如，COVID-19））。本文还涉及含有相同化合物的组合物，以及使用和制备这些化合物的方法。
• Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors
  作者：Dazhi Liu、Zhen Tian、Zhihui Yan、Lixin Wu、Yan Ma、Quan Wang、Wei Liu、Honggang Zhou、Cheng Yang

  DOI：10.1016/j.bmc.2013.03.075

  日期：2013.6

  A number of 1,2-benzisothiazol-3-one derivatives were prepared through structural modification of the original compound from high-throughput screening. Some analogues (e. g., 6b, 6r, 6s and 6w) were identified as novel and potent caspase inhibitors with IC50 of nanomolar. Structure-activity relationship (SAR) studies for caspase-3 inhibition were evaluated in vitro. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The present small molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.
• Potent, Selective, and Orally Available Benzoisothiazolone Phosphomannose Isomerase Inhibitors as Probes for Congenital Disorder of Glycosylation Ia
  作者：Russell Dahl、Yalda Bravo、Vandana Sharma、Mie Ichikawa、Raveendra-Panickar Dhanya、Michael Hedrick、Brock Brown、Justin Rascon、Michael Vicchiarelli、Arianna Mangravita-Novo、Li Yang、Derek Stonich、Ying Su、Layton H. Smith、Eduard Sergienko、Hudson H. Freeze、Nicholas D. P. Cosford

  DOI：10.1021/jm101401a

  日期：2011.5.26

  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.
• 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.
• [EN] BENZOISOTHIAZOLONES AS INHIBITORS OF PHOSPHOMANNOSE ISOMERASE<br/>[FR] BENZOISOTHIAZOLONES EN TANT QU'INHIBITEURS DE PHOSPHOMANNOSE ISOMÉRASE (PMI)
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2011116355A2

  公开（公告）日：2011-09-22

  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.