2-[2-(3-氧代-1,2-苯并噻唑-2-基)乙基]-1,2-苯并噻唑-3-酮 | 64016-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 2-[2-(3-氧代-1,2-苯并噻唑-2-基)乙基]-1,2-苯并噻唑-3-酮
• 英文名称: 2,2'-(ethane-1,2-diyl)dibenzo[d]isothiazol-3(2H)-one
• 英文别名: 2,2'-(ethane-1,2-diyl)bis(benzo[d]isothiazol-3(2H)-one)；1,2-bis(1,2-benzisothiazol-3-on-2-yl)ethane；2,2'-(Ethane-1,2-diyl)di(1,2-benzothiazol-3(2H)-one)；2-[2-(3-oxo-1,2-benzothiazol-2-yl)ethyl]-1,2-benzothiazol-3-one
• CAS: 64016-11-1
• 化学式: C₁₆H₁₂N₂O₂S₂
• 分子量: 328.415
• InChiKey: VNBNGXLQOCVGDL-UHFFFAOYSA-N

物化性质

• 沸点：
  557.7±60.0 °C(Predicted)
• 密度：
  1.461±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  91.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  硫代水杨酸 在 氯化亚砜 、 1,3-二溴-5,5-二甲基海因 作用下， 以 二氯甲烷 为溶剂， 反应 11.5h， 生成 2-[2-(3-氧代-1,2-苯并噻唑-2-基)乙基]-1,2-苯并噻唑-3-酮
  参考文献：
  名称：

  Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy

  摘要：

  Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an important target for anticancer drugs. Selective inhibition of TrxR by 1,2-(bis-1,2-benzisoselenazol-3(2H)-one)ethane (4a) prevents proliferation of several cancer cell lines both in vivo and in vitro. Using the structure of 4a as a starting point, a series of novel bis-1,2-benzisoselenazol-3(2H)-ones was designed, prepared and tested to explore the structure-activity relationships (SARs) for this class of inhibitor and to improve their potency. Notably, 1,2-(5,5'-dimethoxybis(1,2-benzisoselenazol-3(2H)-one))ethane (12) was found to be more potent than 4a in both in vitro and in vivo evaluation. Its binding sites were confirmed by biotin-conjugated iodoacetamide assay and a SAR model was generated to guide further structural modification. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.033

文献信息

• Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects
  作者：P. Gopinath、R.K. Yadav、P.K. Shukla、K. Srivastava、S.K. Puri、K.M. Muraleedharan

  DOI：10.1016/j.bmcl.2017.01.027

  日期：2017.3

  were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had

  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。
• Ebsulfur as a potent scaffold for inhibition and labelling of New Delhi metallo-β-lactamase-1 in vitro and in vivo
  作者：Jianpeng Su、Jiayun Liu、Cheng Chen、Yuejuan Zhang、Kewu Yang

  DOI：10.1016/j.bioorg.2018.11.035

  日期：2019.3

  The superbug infection caused by New Delhi metallo-beta-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a-b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16-9 mu M, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 mu M. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 mu g/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli ECO8 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.
• US4113728A
  申请人：——

  公开号：US4113728A

  公开（公告）日：1978-09-12
• US4212872A
  申请人：——

  公开号：US4212872A

  公开（公告）日：1980-07-15
• US4212979A
  申请人：——

  公开号：US4212979A

  公开（公告）日：1980-07-15