2,3-二氢1,4-二氧六环-6-磺酰胺 | 90222-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 2,3-二氢1,4-二氧六环-6-磺酰胺
• 中文别名: 2,3-二氢-苯并[1,4]二噁英-6-磺酸amide
• 英文名称: 2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
• 英文别名: 2,3-dihydro-benzo[1,4]dioxine-6-sulfonic acid amide；1,4-benzodioxan-6-sulfonamide；2,3-Dihydro-1,4-benzodioxine-6-sulfonamide
• CAS: 90222-81-4
• 化学式: C₈H₉NO₄S
• mdl: MFCD00704682
• 分子量: 215.23
• InChiKey: OAMPULWQGDEOHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  87
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  2,3-二氢1,4-二氧六环-6-磺酰胺 在 sodium dithionite 、 titanium(IV) chloride tetrahydrofuran 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide
  参考文献：
  名称：

  Identification of a Novel Family of BRAF^V600E Inhibitors

  摘要：

  The BRAF oncoprotein is mutated in about half of malignant melanomas and other cancers, and a kinase activating single valine to glutamate substitution at residue 600 (BRAF(V600E)) accounts for over 90% of BRAF-mediated cancers. Several BRAF(V600E) inhibitors have been developed, although they harbor some liabilities, thus motivating the development of other BRAF(V600E) inhibitor options. We report here the use of an ELISA based high-throughput screen to identify a family of related quinolol/naphthol compounds that preferentially inhibit BRAF(V600E) over BRAF(WT) and other kinases. We also report the X-ray crystal structure of a BRAF/quinolol complex revealing the mode of inhibition, employ structure-based medicinal chemistry efforts to prepare naphthol analogues that inhibit BRAF(V600E) in vitro with IC50 values in the 80-200 nM range under saturating ATP concentrations, and demonstrate that these compounds inhibit MAPK signaling in melanoma cells. Prospects for improving the potency and selectivity of these inhibitors are discussed.

  DOI：

  10.1021/jm3004416
• 作为产物：
  描述：

  苯并-1,4-二氧六环-6-硼酸 在 1,4-diazabicyclo[2.2.2]octane-triethylenediamine-bis(sulfur dioxide) 、 四丁基溴化铵 、 palladium diacetate 、 三乙胺 、 hydroxylamine-O-sulfonic acid 作用下， 以 1,4-二氧六环 、 甲醇 、 氘代甲醇-d 、 水 为溶剂， 反应 2.52h， 以56%的产率得到2,3-二氢1,4-二氧六环-6-磺酰胺
  参考文献：
  名称：

  硼酸和DABSO催化钯（II）合成亚磺酸盐：氧化还原中性，无磷化转变

  摘要：

  已经实现了氧化还原中性钯（II）催化的芳基，杂芳基和烯基硼酸到亚磺酸盐中间体的转化，然后再转化为砜和磺酰胺。简单的Pd（OAc）2催化剂与二氧化硫替代1,4-二氮杂双环[2.2.2]辛烷双（二氧化硫）（DABSO）结合使用，足以实现硼酸的快速高产转化率变成相应的亚磺酸盐。然后，基于C或N的亲电试剂的加入可以在一锅，两步过程中分别转化为砜和磺酰胺。

  DOI：

  10.1002/anie.201508370

文献信息

• Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism
  作者：Xin Zhang、Xiao–Qin Lv、Sheng Tang、Lin Mei、Ying–Hong Li、Jing–Pu Zhang、Jian–Dong Jiang、Zong–Gen Peng、Dan–Qing Song

  DOI：10.1016/j.ejmech.2017.12.002

  日期：2018.1

  Aloperine (1), a Chinese natural product with a unique endocyclic scaffold, was first identified to be a potent hepatitis C virus (HCV) inhibitor in our laboratory. Thirty-four new aloperine derivatives were designed, synthesized and evaluated for their anti-HCV activities taking 1 as the lead. Among them, compound 7f exhibited the potential potency with EC50 values in a micromolar range against both

  Aloperine（1）是一种中国天然产物，具有独特的环内支架，在我们的实验室中首次被鉴定为有效的丙型肝炎病毒（HCV）抑制剂。以1为首，设计，合成和评估了34种新的苦瓜碱衍生物的抗HCV活性。其中，化合物7f对野生型和直接作用的抗病毒剂（DAA）耐药变体均表现出潜在的效价，其EC 50值在微摩尔范围内，并且与批准的DAA协同抑制HCV复制。此外，它还具有良好的口服药代动力学和安全性，表明其具有高度的类药物性质。主要机制表明7f可能针对宿主组件，与临床上当前使用的DAA明显不同。因此，我们认为苦参碱衍生物是一类新型的抗HCV药物，化合物7f已被选为有前途的抗病毒候选药物，用于进一步研究。
• Pyrazolines for the Modulation of PKM2
  申请人：Becker Oren M.

  公开号：US20120302609A1

  公开（公告）日：2012-11-29

  The invention relates to pyrazoline substituted compounds and methods for activating PKM2. The compounds and methods are useful in treating or preventing a disease or disorder selected from cancer, cell proliferative disorder, inflammatory disorder, metabolic disorder, and immune system disorder.

  该发明涉及取代吡唑啉化合物和激活PKM2的方法。这些化合物和方法在治疗或预防癌症、细胞增殖紊乱、炎症性疾病、代谢紊乱和免疫系统紊乱等疾病或疾病中具有用途。
• Synthesis of bicyclic aromatic sulfonic acids, sulfonyl chlorides and sulfonamides
  申请人：ELI LILLY AND COMPANY

  公开号：EP0583960A2

  公开（公告）日：1994-02-23

  This invention provides a novel process for the synthesis of bicyclic aromatic sulfonic acids employing reacting a bicyclic aromatic compound with sulfur trioxide-N,N-dimethylformamide complex in the presence of a water miscible, non-reactive solvent. The resulting sulfonic acid may be converted into the corresponding sulfonyl halide by the reaction with a thionyl halide. This invention further provides a novel process for the synthesis of bicyclic aromatic sulfonamides employing the reaction conditions described supra followed by an ammonolysis or amination. The resulting bicyclic aromatic sulfonamides can then be reacted with an appropriately substituted isocyanate to synthesize diaryl sulfonylureas.

  本发明提供了一种新型的合成双环芳香磺酸的方法，其包括在水溶性、非反应性溶剂存在下，将双环芳香化合物与三氧化硫-二甲基甲酰胺复合物反应。所得到的磺酸可以通过与硫代卤化物反应转化为相应的磺酰卤化物。本发明还提供了一种新型的合成双环芳香磺酰胺的方法，其包括在上述反应条件下，经过氨解或胺化反应。所得到的双环芳香磺酰胺可以与适当取代的异氰酸酯反应，合成二芳基磺酰脲。
• Novel Pyridine Compounds
  申请人：Bach Peter

  公开号：US20090227555A2

  公开（公告）日：2009-09-10

  The present invention relates to certain novel pyridin compounds of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-thrombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新型的Formula (I)吡啶化合物，以及制备这些化合物的方法，它们作为P2Y12抑制剂和抗血栓剂等的用途，以及它们的制备过程，它们在心血管疾病中作为药物的用途，以及包含它们的制药组合物。
• ACTIVATORS OF HUMAN PYRUVATE KINASE
  申请人：The United States of America, as represented by the Secretary, Department of Health and Human Serv

  公开号：US20150105395A1

  公开（公告）日：2015-04-16

  Disclosed are pyruvate kinase M2 activators, which are, bis sulfonamide piperazinyl compounds of Formula (I) and 2,4-disubstituted 4H-thieno[3,2-b]pyrrole-2-(substituted benzyl)pyridazin-3(2H)ones of Formula (II), wherein L and R 1 to R 16 are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer and anemia, Formulas (I); (II).

  本发明涉及丙酮酸激酶M2激活剂，其为式（I）的双磺酰胺哌嗪化合物和式（II）的2,4-二取代4H-噻吩[3,2-b]吡咯-2-（取代苯基）吡啶并[3（2H）]酮，其中L和R1至R16如本文所定义，适用于治疗许多可以通过激活PKM2治疗的疾病，例如癌症和贫血，式（I）;（II）。