9-bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene | 1401305-32-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene
• 英文别名: 10-Bromo-9-fluoro-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine；10-bromo-9-fluoro-2-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine
• CAS: 1401305-32-5
• 化学式: C₁₁H₇BrFIN₂O
• 分子量: 408.996
• InChiKey: PJELOMRFWGRHOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 在 tris-(dibenzylideneacetone)dipalladium(0) 正丁基锂 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 hexanes 为溶剂， 反应 22.58h， 生成 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid methyl ester
  参考文献：
  名称：

  BENZOXAZEPIN COMPOUNDS SELECTIVE FOR PI3K P110 DELTA AND METHODS OF USE

  摘要：

  本句翻译为中文是：苯并恶唑啉I型化合物，包括立体异构体、几何异构体、互变异构体、代谢物以及药学上可接受的盐，对于抑制PI3K的δ异构体以及治疗由脂质激酶介导的疾病如炎症、免疫疾病和癌症是有用的。公开了使用I型化合物公式进行体外、原位和体内诊断、预防或治疗哺乳动物细胞中此类疾病或相关病理状况的方法。

  公开号：

  US20120245144A1
• 作为产物：
  描述：

  9-bromo-8-fluoro-2,3-diiodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 在 乙基溴化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 9-bromo-8-fluoro-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene
  参考文献：
  名称：

  Structure-Based Design of Tricyclic NF-κB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K)

  摘要：

  We report here structure-guided optimization of a novel series of NF-kappa B inducing kinase (NIK) inhibitors. Starting from a modestly potent, low molecular weight lead, activity was improved by designing a type 11/2 binding mode that accessed a back pocket past the methionine-471 gatekeeper. Divergent binding modes in NIK and PI3K were exploited to dampen PI3K inhibition while maintaining NIK inhibition within these series. Potent compounds were discovered that selectively inhibit the nuclear translocation of NF-kappa B2 (p52/REL-B) but not canonical NF-kappa B1 (REL-A/p50).

  DOI：

  10.1021/acs.jmedchem.6b01363

文献信息

• [EN] BENZOXAZEPIN COMPOUNDS SELECTIVE FOR PI3K P110 DELTA AND METHODS OF USE<br/>[FR] COMPOSÉS DE BENZOXAZÉPINE SÉLECTIFS POUR PI3K P110 DELTA ET LEURS MÉTHODES D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012126901A1

  公开（公告）日：2012-09-27

  Benzoxazepin Formula (I) compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  BenzoxazePIn Formula (I) 化合物，包括立体异构体、几何异构体、互变异构体、代谢物和药学上可接受的盐，对于抑制PI3K的δ异构体以及治疗由脂质激酶介导的炎症、免疫性疾病和癌症是有用的。本文还揭示了使用Formula (I) 化合物在哺乳动物细胞中进行体外、体内和原位诊断、预防或治疗此类疾病或相关病理情况的方法。
• Benzoxazepin compounds selective for PI3K P110 delta and methods of use
  申请人：Heffron Timothy

  公开号：US09090628B2

  公开（公告）日：2015-07-28

  Benzoxazepin Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  BenzoxazePIn Formula I 化合物，包括立体异构体、几何异构体、互变异构体、代谢物和药学上可接受的盐，用于抑制PI3K的delta亚型，以及用于治疗由脂质激酶介导的疾病，如炎症、免疫性疾病和癌症。本文揭示了使用Formula I化合物进行哺乳动物细胞内、原位和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• TRICYCLIC COMPOUNDS AND METHODS OF USE THEREFOR
  申请人：Genentech, Inc.

  公开号：US20130217666A1

  公开（公告）日：2013-08-22

  The invention relates to novel compounds of Formula I: wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and subscripts m and n each has the meaning as described herein. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

  本发明涉及公式I的新化合物：其中A1，A2，A3，A4，A5，A6，R2，R4，R5，R6，R7，R8和下标m和n的含义如此处所述。公式I的化合物及其制药组合物在治疗观察到NF-kB信号不良或过度激活的疾病和障碍方面是有用的。
• Tricyclic compounds and methods of use therefor
  申请人：Genentech, Inc.

  公开号：US09034866B2

  公开（公告）日：2015-05-19

  The invention relates to novel compounds of Formula I: wherein A1, A2, A3, A4, A5, A6, R2, R4, R5, R6, R7, R8 and subscripts m and n each has the meaning as described herein. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

  本发明涉及式I的新化合物：其中A1，A2，A3，A4，A5，A6，R2，R4，R5，R6，R7，R8和下标m和n的含义如此处所述。式I的化合物及其制备的药物组合物在治疗疾病和障碍方面是有用的，其中观察到NF-kB信号的不良或过度激活。
• US9034866B2
  申请人：——

  公开号：US9034866B2

  公开（公告）日：2015-05-19