3-[hydroxy(phenyl)methylidene]-1,1-dioxo-1λ⁶,2-benzothiazin-4-one | 61018-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 3-[hydroxy(phenyl)methylidene]-1,1-dioxo-1λ⁶,2-benzothiazin-4-one
• 英文别名: (4-hydroxy-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazin-3-yl)-phenyl-methanone；(4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-3-yl)(phenyl)methanone；(4-hydroxy-1,1-dioxido-2H-1,2-benzothiazin-3-yl)(phenyl)methanone；3-benzoyl-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide；3-benzoyl-4-hydroxy-2H-1,2-benzothiazine-1,1-dioxide；3-benzoyl-1,1-dioxo-4-hydroxy-2H-1,2-benzothiazine；3-benzoyl-4-hydroxy-1,2-benzothiazine-1,1-dioxide
• CAS: 61018-80-2
• 化学式: C₁₅H₁₁NO₄S
• 分子量: 301.323
• InChiKey: ZMZZZTDKYPNUNC-UHFFFAOYSA-N

物化性质

• 沸点：
  497.7±55.0 °C(Predicted)
• 密度：
  1.490±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.47
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-[hydroxy(phenyl)methylidene]-1,1-dioxo-1λ⁶,2-benzothiazin-4-one 在 potassium carbonate 、 一水合肼 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 丙酮 、 乙腈 为溶剂， 反应 12.78h， 生成 N'-(2,6-dichlorobenzylidene)-2-(4-methyl-5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-1(4H)-yl)acetohydrazide
  参考文献：
  名称：

  Synthesis, molecular docking and antiviral screening of novel N′-substitutedbenzylidene-2-(4-methyl-5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-1(4H)-yl)acetohydrazides

  摘要：

  N'-Substitutedbenzylidene-2-(4-methyl-5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-1(4H)-yl)acetohydrazides (7a-u) were synthesized through a multistep reaction. The final compounds were screened for anti-HIV-1 and cytotoxic activities. Among these compounds, 7l and 7m exhibited the most significant anti-HIV-1 activity with EC50 values of 5.4 and 3.3 mu M, respectively, while 7j showed moderate anti-HIV activity with an EC50 value 17.1 mu M. Molecular docking into HIV-1 Reverse Transcriptase also showed the best fit for 7l and 7m followed by 7j. In addition, compounds 7b, 7f, 7h, 7k, 7o, and 7s exhibited no toxicity in all the three cell lines used i.e., primary human PBM, CEM, and Vero cells, while 7e, 7g, 7i, 7n, 7p, 7q, and 7t exhibited no cytotoxic activity in primary human PBM cells. Moreover, it was found through molecular docking that compounds 7l, 7m, and 7j bound efficiently in the NTP-binding pocket of HIV-1 Reverse Transcriptase. The structure-activity relationship established on these results would facilitate the further development of new HIV inhibitors based on this skeleton.

  DOI：

  10.1007/s00044-013-0879-7
• 作为产物：
  描述：

  糖精 在 sodium ethanolate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 3-[hydroxy(phenyl)methylidene]-1,1-dioxo-1λ⁶,2-benzothiazin-4-one
  参考文献：
  名称：

  发现环状磺酰胺衍生物作为 SARS-CoV-2 的强效抑制剂

  摘要：

  严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 继续在全球传播，已确诊 2500 万例病例和 80 万人死亡。迫切需要针对 SARS-CoV-2 的有效治疗方法。在本研究中，我们确定了一类环状磺酰胺衍生物作为新型 SARS-CoV-2 抑制剂。合成化合物中的化合物13c对 SARS-CoV-2表现出强大的抑制活性 (IC 50 = 0.88 μM)，没有细胞毒性 (CC 50 > 25 μM)，选择性指数 (SI) 为 30.7。此外，化合物13c在 hERG 和细胞毒性研究中表现出高口服生物利用度 (77%) 和代谢稳定性以及良好的安全性。本研究确定环状磺酰胺衍生物是开发抗 SARS-CoV-2 药物的有希望的新模板。

  DOI：

  10.1016/j.bmcl.2020.127667

文献信息

• Stereopure Functionalized Benzosultams via Ruthenium(II)-Catalyzed Dynamic Kinetic Resolution–Asymmetric Transfer Hydrogenation
  作者：Marko Jeran、Andrej Emanuel Cotman、Michel Stephan、Barbara Mohar

  DOI：10.1021/acs.orglett.7b00670

  日期：2017.4.21

  resolution–asymmetric transfer hydrogenation (DKR–ATH) of α-(N-sulfonylimino) and α-(N-sulfonylamino) aryl ketones to 4-hydroxy-benzo-δ- and 3-(α-hydroxy-arylmethyl)-benzo-γ-sultams is presented. By employing enantiopure ansa-Ru[PipSO2DPEN(CH2)4Ph] cat. II with S/C = 10 000 in a HCO2H/Et3N binary mix, up to >99.9% ee and dr >99:1 are obtained with 100% conversion under mild conditions. Application to access the stereopure

  高度非对映和对映选择性的Ru（II）催化的动态动力学拆分-α-（N-磺酰氨基）和α-（N-磺酰氨基）芳基酮的不对称转移氢化（DKR-ATH）生成4-羟基-苯并-δ -和3-（α-羟基-芳基甲基）-苯并-γ-sulTAms被提出。通过采用对映体纯的柄-Ru [PipSO 2 DPEN（CH 2）4 PH]猫。在HCO 2 H / Et 3 N二元混合物中S / C = 10000的II，在温和条件下以100％的转化率可获得高达> 99.9％ee和dr> 99：1的dr。申请访问立体纯“结构简化的TsDPEN” N，N-配体s yn-3-（α氨基苄基） -苯并-γ-磺内酰胺（“ SYN -ULTAM”）及其结构异构体的反式-4-氨基-3-苯基-苯并-δ-磺内酰胺（反式- 4）是证明。
• Studies on Synthesis of Novel Triazole Tagged Pyrazole Fused Naphthalene 5-Thiazine-5,5-dioxide Derivatives, Their Antimicrobial, and Antioxidant Activity
  作者：G. Malla Reddy、P. Nagender、R. Naresh Kumar、J. H. Ahn、K. Pranay Kumar、A. K. R. Kanugula、K. V. S. Rama Krishna、S. Kotamraju、B. Narsaiah

  DOI：10.1002/jhet.2013

  日期：2014.8

  A series of novel triazole tagged pyrazole fused naphthalene-5-thiazine-5,5-dioxide derivatives and were synthesized starting from sodium salt of saccharin . The structure of each intermediate and products was established on the basis of spectroscopy data. All the synthesized compounds and were screened against various bacterial and fungal strains but found to show no activity up to 150-µg/mL concentration

  一系列新型的三唑标记的吡唑稠合萘-5-噻嗪-5,5-二氧化物衍生物 和 从糖精钠盐开始合成 。根据光谱数据确定每种中间体和产物的结构。所有合成的化合物 和 对各种细菌和真菌菌株进行了筛选，但发现在浓度高达150 µg / mL时无活性。进一步筛选抗氧化剂性能得到了有希望的化合物。
• Synthesis and α-Glucosidase Inhibition Activity of 2-[3-(Benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl]-N-arylacetamides: An In Silico and Biochemical Approach
  作者：Furqan Ahmad Saddique、Sana Aslam、Matloob Ahmad、Usman Ali Ashfaq、Muhammad Muddassar、Sadia Sultan、Saman Taj、Muzammil Hussain、Dae Sung Lee、Magdi E. A. Zaki

  DOI：10.3390/molecules26103043

  日期：——

  Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.

  糖尿病（DM）是一种慢性疾病，已经影响了全球大量人口。胰岛素产量不足导致血糖水平升高，从而引发糖尿病。为了降低血糖水平，使用了各种药物来阻断α-葡萄糖苷酶的活性，该酶被认为是将多糖分解为单糖，导致肠道血糖水平升高的原因。我们合成了新型的2-(3-(苯甲酰/对溴苯甲酰)-4-羟基-1,1-二氧化-2H-苯并[e][1,2]噻嗪-2-基)-N-芳基乙酰胺，并对它们进行了体外和体内α-葡萄糖苷酶抑制活性的筛选。衍生物11c、12a、12d、12e和12g显示出对α-葡萄糖苷酶的强效抑制作用。这些化合物在体外筛选过程中表现出良好的对接得分，并与所选残基（Asp203、Asp542、Asp327、His600、Arg526）展现出优秀的结合相互作用。同样，这些化合物在体内也表现出良好的α-葡萄糖苷酶抑制作用，其IC50值分别为30.65、18.25、20.76、35.14和24.24 μM，优于标准药物阿卡波糖（IC50 = 58.8 μM）。此外，在体内和体外研究模式之间观察到了良好的一致性。
• Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors
  作者：Sana Aslam、Sumera Zaib、Matloob Ahmad、John M. Gardiner、Aqeel Ahmad、Abdul Hameed、Norbert Furtmann、Michael Gütschow、Jürgen Bajorath、Jamshed Iqbal

  DOI：10.1016/j.ejmech.2014.03.035

  日期：2014.5

  efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)

  从糖精钠盐开始有效地合成了两个系列的新型基于吡唑并苯并噻嗪的杂化化合物。通过使用对氟苯甲醛对吡唑并[4,3- c ] [1,2]苯并噻嗪支架进行N-芳基化，然后通过亚芳基二胺处理引入苯并咪唑或类似的环系统。研究了这些与亚苯基连接的杂化化合物作为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的潜在抑制剂。化合物12d和12k是最有效的AChE抑制剂，IC 50值分别为11和13 nM，而6j（IC 50 = 17 nM）被证明是最有效的BuChE抑制剂，对BuChE的选择性比AChE高。还对人的AChE和BuChE进行了分子对接研究，以表明可能的结合方式，其中抑制剂的延伸结构沿两种酶的活性位点排列。
• Identification of Cyclicsulfonamide Derivatives with an Acetamide Group as 11.BETA.-Hydroxysteroid Dehydrogenase 1 Inhibitors
  作者：Se Hoan Kim、Sung Wook Kwon、So Young Chu、Jae Hong Lee、Banda Narsaiah、Chi Hyun Kim、Seung Kyu Kang、Nam Sook Kang、Sang Dal Rhee、Myung Ae Bae、Sung Hoon Ahn、Duck Chan Ha、Ki Young Kim、Jin Hee Ahn

  DOI：10.1248/cpb.59.46

  日期：——

  dehydrogenase type 1 (11β-HSD1) inhibitor research, cyclic sulfonamide derivatives with an acetamide group at the 2-position were synthesized and evaluated for their abilities to inhibit 11β-HSD1. Among this series, Compound 34 showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, good pharmacokinetic and safety profiles human ether-a-go-go related gene (hERG

  在我们继续进行1β-羟基类固醇脱氢酶1型（11β-HSD1）抑制剂研究的过程中，合成了在2位带有乙酰胺基的环状磺酰胺衍生物，并评估了其抑制11β-HSD1的能力。在该系列化合物中，化合物34对人11β-HSD1具有良好的体外活性，对11β-HSD2的选择性，微粒体稳定性，良好的药代动力学和安全性与人随行相关的基因（hERG和细胞色素P450（CYP）） 。此外，对接研究解释了人类和小鼠11β-HSD1之间的活性差异。