2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-(1,1-dioxo-S-thiomorpholin-4-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene | 1282524-08-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-(1,1-dioxo-S-thiomorpholin-4-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene
• 英文别名: 4-[4-[2-(2,4-Difluorophenyl)-1,2,4-triazol-3-yl]-9-oxa-3-thia-14-azatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),4,11,13-pentaen-13-yl]-1,4-thiazinane 1,1-dioxide
• CAS: 1282524-08-6
• 化学式: C₂₃H₁₉F₂N₅O₃S₂
• 分子量: 515.564
• InChiKey: HVYKBFOGAMNSHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-噻吩乙酸 在 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane 、 palladium diacetate 、 三苯基膦 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 正丁基锂 、 偶氮二甲酸二异丙酯 、 四乙基氯化铵 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 11.0h， 生成 2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-(1,1-dioxo-S-thiomorpholin-4-yl)-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene
  参考文献：
  名称：

  BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

  摘要：

  Formula I中的苯并氧杂环化合物，包括立体异构体、几何异构体、互变异构体、溶剂化合物、代谢物和其药学上可接受的盐，其中：Z1为CR1或N；Z2为CR2或N；Z3为CR3或N；Z4为CR4或N；其中（i）X1为N且X2为S，（ii）X1为S且X2为N，（iii）X1为CR7且X2为S，（iv）X1为S且X2为CR7；（v）X1为NR8且X2为N，（vi）X1为N且X2为NR8，（vii）X1为CR7且X2为O，（viii）X1为O且X2为CR7，（ix）X1为CR7且X2为C(R7)2，（x）X1为C(R7)2且X2为CR7；（xi）X1为N且X2为O，或（xii）X1为O且X2为N，用于抑制脂质激酶，包括p110α和PI3K的其他同工酶，并用于治疗由脂质激酶介导的癌症等疾病。公开了利用Formula I中的化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理状况的方法。

  公开号：

  US20110076291A1

文献信息

• US8263633B2
  申请人：——

  公开号：US8263633B2

  公开（公告）日：2012-09-11
• US8673952B2
  申请人：——

  公开号：US8673952B2

  公开（公告）日：2014-03-18
• US8952043B2
  申请人：——

  公开号：US8952043B2

  公开（公告）日：2015-02-10
• [EN] BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS DE BENZOXÉPINE INHIBITEURS DE PI3K ET LEURS PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011036284A1

  公开（公告）日：2011-03-31

  Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of P13K, and for treating disorders such as cancer mediated by lipid kinases. 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.
• BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Blaquiere Nicole

  公开号：US20110076291A1

  公开（公告）日：2011-03-31

  Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z 1 is CR 1 or N; Z 2 is CR 2 or N; Z 3 is CR 3 or N; Z 4 is CR 4 or N; and where (i) X 1 is N and X 2 is S, (ii) X 1 is S and X 2 is N, (iii) X 1 is CR 7 and X 2 is S, (iv) X 1 is S and X 2 is CR 7 ; (v) X 1 is NR 8 and X 2 is N, (vi) X 1 is N and X 2 is NR 8 , (vii) X 1 is CR 7 and X 2 is O, (viii) X 1 is O and X 2 is CR 7 , (ix) X 1 is CR 7 and X 2 is C(R 7 ) 2 , (x) X 1 is C(R 7 ) 2 and X 2 is CR 7 ; (xi) X 1 is N and X 2 is O, or (xii) X 1 is O and X 2 is N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. 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.

  Formula I中的苯并氧杂环化合物，包括立体异构体、几何异构体、互变异构体、溶剂化合物、代谢物和其药学上可接受的盐，其中：Z1为CR1或N；Z2为CR2或N；Z3为CR3或N；Z4为CR4或N；其中（i）X1为N且X2为S，（ii）X1为S且X2为N，（iii）X1为CR7且X2为S，（iv）X1为S且X2为CR7；（v）X1为NR8且X2为N，（vi）X1为N且X2为NR8，（vii）X1为CR7且X2为O，（viii）X1为O且X2为CR7，（ix）X1为CR7且X2为C(R7)2，（x）X1为C(R7)2且X2为CR7；（xi）X1为N且X2为O，或（xii）X1为O且X2为N，用于抑制脂质激酶，包括p110α和PI3K的其他同工酶，并用于治疗由脂质激酶介导的癌症等疾病。公开了利用Formula I中的化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理状况的方法。