Methyl 4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxylate | 126522-03-0

• 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: Methyl 4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxylate
• CAS: 126522-03-0
• 化学式: C₁₄H₁₂O₃S
• 分子量: 260.313
• InChiKey: OQEAITNURRBDQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  63.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxylate 在 4-二甲氨基吡啶 、 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide
  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：

  3,4-二氢-2H-苯并[b]噁嗪-5-酮 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Methyl 4,5-dihydrothieno[3,2-d][1]benzoxepine-2-carboxylate
  参考文献：
  名称：

  Structure-based design of thienobenzoxepin inhibitors of PI3-kinase

  摘要：

  Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.124

文献信息

• Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform
  作者：Timothy P. Heffron、BinQing Wei、Alan Olivero、Steven T. Staben、Vickie Tsui、Steven Do、Jennafer Dotson、Adrian J. Folkes、Paul Goldsmith、Richard Goldsmith、Janet Gunzner、John Lesnick、Cristina Lewis、Simon Mathieu、Jim Nonomiya、Stephen Shuttleworth、Daniel P. Sutherlin、Nan Chi Wan、Shumei Wang、Christian Wiesmann、Bing-Yan Zhu

  DOI：10.1021/jm2007084

  日期：2011.11.24

  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.
• SEKHAR, B. CHANDRA;RAMANA, D. V.;RAMADAS, S. R., SULFUR LETT., 9,(1989) N, C. 271-277
  作者：SEKHAR, B. CHANDRA、RAMANA, D. V.、RAMADAS, S. R.

  DOI：——

  日期：——
• Structure-based design of thienobenzoxepin inhibitors of PI3-kinase
  作者：Steven T. Staben、Michael Siu、Richard Goldsmith、Alan G. Olivero、Steven Do、Daniel J. Burdick、Timothy P. Heffron、Jenna Dotson、Daniel P. Sutherlin、Bing-Yan Zhu、Vickie Tsui、Hoa Le、Leslie Lee、John Lesnick、Cristina Lewis、Jeremy M. Murray、Jim Nonomiya、Jodie Pang、Wei Wei Prior、Laurent Salphati、Lionel Rouge、Deepak Sampath、Steve Sideris、Christian Wiesmann、Ping Wu

  DOI：10.1016/j.bmcl.2011.04.124

  日期：2011.7

  Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.