2-[(2-chlorophenyl)methylcarbamoyl]-4,5-dihydro-6-oxa-1-thiabenzo[e]azulene-8-carboxylic acid methyl ester | 1189810-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(2-chlorophenyl)methylcarbamoyl]-4,5-dihydro-6-oxa-1-thiabenzo[e]azulene-8-carboxylic acid methyl ester
• 英文别名: methyl 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate；2-[(2-Chloro-phenyl)-methyl-carbamoyl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-8-carboxylic acid methyl ester；methyl 2-[(2-chlorophenyl)-methylcarbamoyl]-4,5-dihydrothieno[3,2-d][1]benzoxepine-8-carboxylate
• CAS: 1189810-56-7
• 化学式: C₂₂H₁₈ClNO₄S
• 分子量: 427.908
• InChiKey: OPKCZGPVBYJGIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2-chlorophenyl)methylcarbamoyl]-4,5-dihydro-6-oxa-1-thiabenzo[e]azulene-8-carboxylic acid methyl ester 在 吡啶 、 氯化亚砜 、 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 N2-(2-chlorophenyl)-N8-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide
  参考文献：
  名称：

  Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

  摘要：

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

  DOI：

  10.1021/jm2007084
• 作为产物：
  描述：

  8-溴-3,4-二氢-2H-苯并[b]氧杂环庚三烯-5-酮 在 1,1'-双(二苯基膦)二茂铁 、 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 palladium diacetate 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 53.0h， 生成 2-[(2-chlorophenyl)methylcarbamoyl]-4,5-dihydro-6-oxa-1-thiabenzo[e]azulene-8-carboxylic acid methyl ester
  参考文献：
  名称：

  Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

  摘要：

  Of the four class I phosphoinositide 3-kinase (PI3K) isoforms, PI3k alpha has justly received the most attention for its potential in cancer therapy. Herein we report our successful approaches to achieve PI3K alpha vs PI3K beta selectivity for two chemical series. In the thienopyrimidine series of inhibitors, we propose that select ligands achieve selectivity derived from a hydrogen bonding interaction with Arg770 of PI3K alpha that is not attained with the corresponding Lys777 of PI3K beta. In the benzoxepin series of inhibitors, the selectivity observed can be rationalized by the difference in electrostatic potential between the two isoforms in a given region rather than any specific interaction.

  DOI：

  10.1021/jm2007084

文献信息

• BENZOPYRAN AND BENZOXEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Do Steven

  公开号：US20090247567A1

  公开（公告）日：2009-10-01

  Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, 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 Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Benzopyran和benzoxepin的化合物I和II的分子式，包括其立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括p110 alpha和PI3K的其他同系物，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用分子式I和II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条件的方法。
• Benzopyran and benzoxepin PI3K inhibitor compounds and methods of use
  申请人：Genentech, Inc.

  公开号：US07928248B2

  公开（公告）日：2011-04-19

  Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, 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 Formulas I and II 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和II的苯并吡喃和苯并氧杂环化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括p110α和其他PI3K同系物，并用于治疗由脂质激酶介导的癌症等疾病。公开了使用公式I和II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。
• 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene compounds
  申请人：Do Steven

  公开号：US08399690B2

  公开（公告）日：2013-03-19

  Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, 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 Formulas I and II 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和II中的苯并吡喃和苯并氧杂环化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和其药学上可接受的盐，可用于抑制脂质激酶，包括p110α和其他PI3K同系物，并用于治疗由脂质激酶介导的癌症等疾病。本文揭示了使用公式I和II化合物的方法，用于哺乳动物细胞中的体外、体内诊断、预防或治疗此类疾病或相关病理条件。
• EP2276767B1
  申请人：——

  公开号：EP2276767B1

  公开（公告）日：2014-05-07
• US7928248B2
  申请人：——

  公开号：US7928248B2

  公开（公告）日：2011-04-19