2-(tert-butyloxycarbonylamino)benzo[d]isothiazol-3(2H)-one | 200421-26-7

• 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: 2-(tert-butyloxycarbonylamino)benzo[d]isothiazol-3(2H)-one
• 英文别名: tert-butyl (3-oxobenzo[d]isothiazol-2(3H)-yl)carbamate；tert-butyl N-(3-oxo-1,2-benzothiazol-2-yl)carbamate
• CAS: 200421-26-7
• 化学式: C₁₂H₁₄N₂O₃S
• 分子量: 266.321
• InChiKey: HQHHTNUYJNCVLC-UHFFFAOYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(tert-butyloxycarbonylamino)benzo[d]isothiazol-3(2H)-one 在 盐酸 、 acetate buffer 、 三氯乙酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.5h， 生成 2-[(4-fluorophenyl)methylideneamino]-1,2-benzothiazol-3-one
  参考文献：
  名称：

  2-（亚苄基-氨基）-苯并[d]异噻唑-3-酮的合成及抗菌性能。

  摘要：

  通过肉汤稀释法确定2-氨基-苯并[d]异噻唑-3-酮和几种在第二位置带有取代或未取代的芳环或芳基亚烯基部分的2-亚芳基氨基衍生物的体外抗菌活性选择菌株来定义其光谱和效价。所有化合物都表现出对枯草芽孢杆菌，链球菌，肠球菌和葡萄球菌（包括耐青霉素的临床分离株）的良好抗菌性能。几种化合物对化脓性链球菌具有极好的抑制特性，而化脓性链球菌是测试过的最敏感的微生物。许多苯并异噻唑酮对革兰阴性流感嗜血杆菌表现出良好的活性。关于抗真菌活性，几种受试化合物在3-6微克ml-1的浓度下可抑制酿酒酵母。在所有情况下，母体2-氨基-苯并[d]异噻唑-3-酮是最有效的药物，最小抑菌浓度（MIC）值范围为0.07至6微克ml-1。获得的结果表明，这些化合物大多数是广谱抗菌物质，并且是抗青霉素耐药葡萄球菌的有前途的药物。

  DOI：

  10.1016/j.ejmech.2003.11.004
• 作为产物：
  描述：

  2, 2'-二硫代二苯甲酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 38.0h， 生成 2-(tert-butyloxycarbonylamino)benzo[d]isothiazol-3(2H)-one
  参考文献：
  名称：

  Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines

  摘要：

  We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b01679

文献信息

• Vicini, Paola; Manotti, Cesare; Caretta, Antonio, Arzneimittel-Forschung/Drug Research, 1997, vol. 47, # 11, p. 1218 - 1221
  作者：Vicini, Paola、Manotti, Cesare、Caretta, Antonio、Amoretti, Loredana

  DOI：——

  日期：——
• Hybrid molecules between benzenesulfonamides and active antimicrobial benzo[d]isothiazol-3-ones
  作者：Franca Zani、Matteo Incerti、Rocco Ferretti、Paola Vicini

  DOI：10.1016/j.ejmech.2008.07.022

  日期：2009.6

  Novel hybrid molecules between benzenesulfonamides and active antimicrobial 2-amino-benzo[d]isothiazol-3-ones were synthesized and characterised and their in vitro antimicrobial activity was evaluated by the minimal inhibitory concentration (MIC). The compounds exhibit moderate antibacterial properties against Gram-positive bacteria (MIC 6-100 mu g ml(-1)) such as several bacilli, staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains, while no inhibition of Gram-negative Escherichia coli is detected up to the concentration of 100 mu g ml(-1). Synergistic inhibitory activity occurs when sulfanilamides 4a and 4c are tested in combination with trimethoprim against S. aureus. Concerning antifungal properties, only compound 4c is able to inhibit the growth of Saccharomyces cerevisiae and Cryptococcus neoformans yeasts and several dermatophytes. Structure-activity relationships are discussed. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines
  作者：Riccardo Castelli、Laura Scalvini、Federica Vacondio、Alessio Lodola、Mattia Anselmi、Stefano Vezzosi、Caterina Carmi、Michele Bassi、Francesca Ferlenghi、Silvia Rivara、Ingvar R. Møller、Kasper D. Rand、Jennifer Daglian、Don Wei、Emmanuel Y. Dotsey、Faizy Ahmed、Kwang-Mook Jung、Nephi Stella、Simar Singh、Marco Mor、Daniele Piomelli

  DOI：10.1021/acs.jmedchem.9b01679

  日期：2020.2.13

  We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.
• Synthesis and antimicrobial properties of 2-(benzylidene-amino)-benzo[d]isothiazol-3-ones
  作者：Franca Zani、Paola Vicini、Matteo Incerti

  DOI：10.1016/j.ejmech.2003.11.004

  日期：2004.2

  in vitro antimicrobial activity of 2-amino-benzo[d]isothiazol-3-one and of several 2-arylideneamino derivatives carrying in the second position a substituted or unsubstituted aromatic ring or an arylalkenylidene moiety was determined by the broth dilution method against several strains selected to define their spectrum and potency. All the compounds demonstrated good antibacterial properties against

  通过肉汤稀释法确定2-氨基-苯并[d]异噻唑-3-酮和几种在第二位置带有取代或未取代的芳环或芳基亚烯基部分的2-亚芳基氨基衍生物的体外抗菌活性选择菌株来定义其光谱和效价。所有化合物都表现出对枯草芽孢杆菌，链球菌，肠球菌和葡萄球菌（包括耐青霉素的临床分离株）的良好抗菌性能。几种化合物对化脓性链球菌具有极好的抑制特性，而化脓性链球菌是测试过的最敏感的微生物。许多苯并异噻唑酮对革兰阴性流感嗜血杆菌表现出良好的活性。关于抗真菌活性，几种受试化合物在3-6微克ml-1的浓度下可抑制酿酒酵母。在所有情况下，母体2-氨基-苯并[d]异噻唑-3-酮是最有效的药物，最小抑菌浓度（MIC）值范围为0.07至6微克ml-1。获得的结果表明，这些化合物大多数是广谱抗菌物质，并且是抗青霉素耐药葡萄球菌的有前途的药物。