5-氟-3,4-二氢-2H-1,4-苯并恶嗪 | 1067171-66-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 5-氟-3,4-二氢-2H-1,4-苯并恶嗪
• 英文名称: 5-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine
• 英文别名: 5-Fluoro-3,4-dihydro-2H-1,4-benzoxazine
• CAS: 1067171-66-7
• 化学式: C₈H₈FNO
• mdl: MFCD11878397
• 分子量: 153.156
• InChiKey: GAQHKLQOTXHQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-氟-3,4-二氢-2H-1,4-苯并恶嗪 在 氯磺酸 、 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 4.83h， 生成 4-(2-cyano-4-(trifluoromethyl)phenyl)-5-fluoro-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide
  参考文献：
  名称：

  The discovery of benzoxazine sulfonamide inhibitors of Na V 1.7: Tools that bridge efficacy and target engagement

  摘要：

  The voltage-gated sodium channel Na(V)1.7 has received much attention from the scientific community due to compelling human genetic data linking gain-and loss-of-function mutations to pain phenotypes. Despite this genetic validation of Na(V)1.7 as a target for pain, high quality pharmacological tools facilitate further understanding of target biology, establishment of target coverage requirements and subsequent progression into the clinic. Within the sulfonamide class of inhibitors, reduced potency on rat Na(V)1.7 versus human Na(V)1.7 was observed, rendering in vivo rat pharmacology studies challenging. Herein, we report the discovery and optimization of novel benzoxazine sulfonamide inhibitors of human, rat and mouse Na(V)1.7 which enabled pharmacological assessment in traditional behavioral rodent models of pain and in turn, established a connection between formalin-induced pain and histamine-induced pruritus in mice. The latter represents a simple and efficient means of measuring target engagement. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.05.070
• 作为产物：
  描述：

  1,2-二溴乙烷 、 2-氨基-3-氟苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以22 %的产率得到5-氟-3,4-二氢-2H-1,4-苯并恶嗪
  参考文献：
  名称：

  含氮稠环类衍生物、药物组合物及其制备方法和应用

  摘要：

  本发明提供了一种式I所示的氮稠环类衍生物、药物组合物及其制备方法和应用。该化合物具有良好的GnRH受体拮抗作用，具有更长的半衰期，可用于治疗或预防与性腺激素有关的病症和疾病，以及制备用于此类病症和疾病的药物。

  公开号：

  CN115232144A

文献信息

• [EN] DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS<br/>[FR] INHIBITEURS DES CANAUX SODIQUES DE TYPE DIHYDROBENZOXAZINE ET TÉTRAHYDROQUINOXALINE
  申请人：AMGEN INC

  公开号：WO2013122897A1

  公开（公告）日：2013-08-22

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了式I的化合物或其药学上可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病，如疼痛障碍，是有用的。还提供了含有本发明化合物的药物组合物。
• HIV REPLICATION INHIBITOR
  申请人：Shionogi & Co., Ltd.

  公开号：US20140249306A1

  公开（公告）日：2014-09-04

  The present invention provides a novel compound having an antiviral action, in particular, an HIV replication inhibiting action, as well as a pharmaceutical composition, in particular, an anti-HIV agent. wherein, a broken line means the presence or absence of a bond; R 1 is substituted or unsubstituted alkyl etc., R 2 is substituted or unsubstituted alkyloxy etc.; n is 1 or 2; R 3 is a substituted or unsubstituted aromatic carbocyclic group; R 4 is a hydrogen atom etc.; R 5 is a substituted or unsubstituted aromatic carbocyclic group etc.; Y is a single bond etc.; R 6 is substituted or unsubstituted alkyl; R 7 is —Z—R 71 etc.; Z is —NR 72 —CO— etc.; R 71 is substituted or unsubstituted alkyl etc.; R 72 is a hydrogen atom etc.

  本发明提供了一种具有抗病毒作用的新化合物，特别是具有抑制HIV复制作用的化合物，以及一种药物组合物，特别是一种抗HIV药物。其中，虚线表示键的存在或不存在；R1是取代或未取代的烷基等，R2是取代或未取代的烷氧基等；n为1或2；R3是取代或未取代的芳香环烷基；R4是氢原子等；R5是取代或未取代的芳香环烷基等；Y是单键等；R6是取代或未取代的烷基；R7是—Z—R71等；Z是—NR72—CO—等；R71是取代或未取代的烷基等；R72是氢原子等。
• DIHYDROBENZOXAZINE AND TETRAHYDROQUINOXALINE SODIUM CHANNEL INHIBITORS
  申请人：AMGEN INC.

  公开号：US20150057271A1

  公开（公告）日：2015-02-26

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了I式化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav1.7。这些化合物对于治疗可通过钠通道抑制治疗的疾病如疼痛症状是有用的。还提供了含有本发明化合物的药物组合物。
• Dihydrobenzoxazine and tetrahydroquinoxaline sodium channel inhibitors
  申请人：AMGEN INC.

  公开号：US09346798B2

  公开（公告）日：2016-05-24

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了I式化合物或其药学上可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病，如疼痛障碍，是有用的。还提供了含有本发明化合物的制药组合物。
• Heterocyclic compounds useful as Pim kinase inhibitors
  申请人：Incyte Corporation

  公开号：US10450296B2

  公开（公告）日：2019-10-22

  The present application is concerned with heterocyclic compounds that inhibit the activity of Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancers and other diseases.

  本申请涉及抑制 Pim 激酶活性的杂环化合物，这些化合物可用于治疗与 Pim 激酶活性有关的疾病，包括癌症和其他疾病。