3-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester | 1282531-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: 3-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 3-[4-[2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-4,5-dihydro-[1]benzoxepino[5,4-d][1,3]thiazol-8-yl]pyrazol-1-yl]azetidine-1-carboxylate
• CAS: 1282531-40-1
• 化学式: C₂₈H₃₃N₇O₃S
• 分子量: 547.681
• InChiKey: ULEBHHWYGPQVQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  128
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  8-Bromo-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 、 3-(4-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-1H-吡唑-1-基)氮杂丁烷-1-羧酸叔丁酯 以to give 3-{4-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester which的产率得到3-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-pyrazol-1-yl}-azetidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

  摘要：

  公式I中的苯并噻吩化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、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；当(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，对于抑制脂质激酶，包括p110α和其他PI3K的亚型，并用于治疗由脂质激酶介导的癌症等疾病有用。本文还公开了使用公式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条件的方法。

  公开号：

  US20110076291A1

文献信息

• Benzoxepin PI3K inhibitor compounds and methods of use
  申请人：F. Hoffman-La Roche AG

  公开号：US08263633B2

  公开（公告）日：2012-09-11

  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 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.

  公式I中的苯并噁唑化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，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，对于抑制脂质激酶包括p110α和其他PI3K的亚型，并用于治疗由脂质激酶介导的癌症等疾病是有用的。公式I化合物的使用方法，用于哺乳动物细胞中的体外、原位和体内诊断、预防或治疗此类疾病，或相关的病理条件。
• Benzoxepin pi3k inhibitor compounds and methods of use
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2784078A1

  公开（公告）日：2014-10-01

  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 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.

  式 I 的苯氧西泮化合物，包括其立体异构体、几何异构体、同分异构体、溶 剂、代谢物和药学上可接受的盐，其中：Z1 是 CR1 或 N；Z2 是 CR2 或 N；Z3 是 CR3 或 N；Z4 是 CR4 或 N；以及 其中：(i) X1 是 N，X2 是 S；(ii) X1 是 S，X2 是 N；(iii) X1 是 CR7，X2 是 S；(iv) X1 是 S，X2 是 CR7；(v) X1 是 NR8，X2 是 N，(vi) X1 是 N，X2 是 NR8，(vii) X1 是 CR7，X2 是 O，(viii) X1 是 O，X2 是 CR7，(ix) X1 是 CR7，X2 是 C(R7)2，(x) X1 是 C(R7)2，X2 是 CR7；(xi) X1 是 N，X2 是 O，或 (xii) X1 是 O，X2 是 N，这些化合物可用于抑制脂质激酶，包括 p110 alpha 和 PI3K 的其他同工型，以及治疗由脂质激酶介导的疾病，如癌症。公开了使用式 I 化合物体外、原位和体内诊断、预防或治疗哺乳动物细胞中的此类疾病或相关病理状况的方法。
• 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