5-bromo-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide | 155983-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 5-bromo-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide
• 英文别名: 5-bromo-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-one
• CAS: 155983-98-5
• 化学式: C₇H₅BrN₂O₃S
• 分子量: 277.098
• InChiKey: UNWFVIMGKIDJKB-UHFFFAOYSA-N

物化性质

• 密度：
  1.877±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide 在 硫酸 、 sodium hydride 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成 1-benzyl-3-(5-bromo-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,8-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Inhibitors of HCV NS5B polymerase: Synthesis and structure–activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring

  摘要：

  A series of non-nucleoside HCV NS5B polymerase inhibitors based on the N-1-benzyl or N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine core substituted in the D-ring aromatic moiety have been prepared and evaluated. Aromatic substituents extending from position 7 of the D-ring exhibited excellent potency against both genotypes 1a and 1b. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.022
• 作为产物：
  描述：

  在 aluminum (III) chloride 作用下， 反应 0.75h， 生成 5-bromo-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide
  参考文献：
  名称：

  “A Sweet Combination”: Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII

  摘要：

  The sweeteners saccharin (SAC) and acesulfame K (ACE) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design strategy is here reported, which took SAC and ACE as leads and produced a series of 2H-benzo [e][1,2,4]thiadiazin-3(4H)-one-1,1-dioxides (BTD). Many derivatives showed greater potency (K(I)s-CA IX 19.1-408.5 nM) and selectivity (II/IX SI 2-76) than the leads (K(I)s-CA IX 103, 2400 nM; II/IX-SI 56, >4) against CA IX/XII over off-target isoforms. A thorough X-ray crystallographic study depicted their binding mode to both CA II and IX-mimic. The most representative BTDs were characterized in vitro for their antitumor activity against A549, PC-3, and HCT-116 cancer cell lines both in normoxia and hypoxia. The two most effective compounds were assayed for their effect on several apoptosis markers, identifying promising leads for the development of new anticancer drugs.

  DOI：

  10.1021/acs.jmedchem.9b01669

文献信息

• [EN] METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016206101A1

  公开（公告）日：2016-12-29

  The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及一种属于金属β-内酰胺酶抑制剂的I式化合物，以及这种化合物的合成和将其与β-内酰胺类抗生素一起用于克服耐药性的用途。
• Metallo-β-lactamase inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10227331B2

  公开（公告）日：2019-03-12

  The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and RB are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

  本发明涉及式 I 的金属-β-内酰胺酶抑制剂化合物： (I) 及其药学上可接受的盐，其中 Z、RA、X1、X2 和 RB 如本文所定义。本发明还涉及组合物，该组合物包含本发明的金属-β-内酰胺酶抑制剂化合物或其药学上可接受的盐，以及药学上可接受的载体，可选择与β-内酰胺抗生素和/或β-内酰胺酶抑制剂结合使用。本发明进一步涉及治疗细菌感染的方法，包括向患者施用治疗有效量的本发明化合物，与治疗有效量的一种或多种β-内酰胺类抗生素联合使用，也可选择与一种或多种β-内酰胺酶抑制剂化合物联合使用。本发明的化合物在本文所述的克服抗生素耐药性的方法中是有用的。
• METALLO-BETA-LACTAMASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3313828A1

  公开（公告）日：2018-05-02
• EBNA1 INHIBITORS AND THEIR METHOD OF USE
  申请人：THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY

  公开号：US20160289185A1

  公开（公告）日：2016-10-06

  The invention provides EBNA1 inhibitors, and pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by EBNA1 activity such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The compounds and compositions of the invention are further useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection. The compounds and compositions of the invention are further useful for the treatment of diseases caused by lytic EBV infection.
• US9856214B2
  申请人：——

  公开号：US9856214B2

  公开（公告）日：2018-01-02