{(S)-4-[4-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)phenyl]-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl}acetic acid ethyl ester | 916493-47-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: {(S)-4-[4-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)phenyl]-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl}acetic acid ethyl ester
• 英文别名: ethyl (S)-{4-[4-(5,5-dimethyl[1,3,2]dioxaborinane-2-yl)phenyl]-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate；ethyl 2-[(9S)-7-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate
• CAS: 916493-47-5
• 化学式: C₂₆H₃₁BN₄O₄S
• 分子量: 506.434
• InChiKey: VWWPVLQVXRWDCN-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  {(S)-4-[4-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)phenyl]-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl}acetic acid ethyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 、 caesium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 丁酮 为溶剂， 反应 10.0h， 生成 ethyl 2-[(9S)-7-{4-[4-(3-{3-[(2-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanamido}ethyl)disulfanyl]propanamido}propoxy)-3-cyanophenyl]phenyl}-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate
  参考文献：
  名称：

  A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor

  摘要：

  A phenotypic screening of thienodiazepines derived from a hit compound found through a binding assay targeting co-stimulatory molecules on T cells and antigen presenting cells successfully led to the discovery of a thienotriazolodiazepine compound (7f) possessing potent immunosuppressive activity. A chemical biology approach has succeeded in revealing that 7f is a first inhibitor of epigenetic bromodomain-containing proteins. 7f is expected to become an anti-cancer agent as well as an immunosuppressive agent. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.084
• 作为产物：
  描述：

  [(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl]acetic acid ethyl ester 、 联硼酸新戊二醇酯 在 双(三环己基膦)二氯化钯 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以100%的产率得到{(S)-4-[4-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)phenyl]-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl}acetic acid ethyl ester
  参考文献：
  名称：

  A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor

  摘要：

  A phenotypic screening of thienodiazepines derived from a hit compound found through a binding assay targeting co-stimulatory molecules on T cells and antigen presenting cells successfully led to the discovery of a thienotriazolodiazepine compound (7f) possessing potent immunosuppressive activity. A chemical biology approach has succeeded in revealing that 7f is a first inhibitor of epigenetic bromodomain-containing proteins. 7f is expected to become an anti-cancer agent as well as an immunosuppressive agent. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.084

文献信息

• THIENOTRIAZOLODIAZEPINE COMPOUND AND A MEDICINAL USE THEREOF
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP1887008B1

  公开（公告）日：2021-04-21
• A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor
  作者：Junichi Endo、Hidemasa Hikawa、Maiko Hamada、Seigo Ishibuchi、Naoto Fujie、Naoki Sugiyama、Minoru Tanaka、Haruhito Kobayashi、Kunio Sugahara、Koichi Oshita、Kazunori Iwata、Shinsuke Ooike、Meguru Murata、Hiroshi Sumichika、Kenji Chiba、Kunitomo Adachi

  DOI：10.1016/j.bmcl.2016.01.084

  日期：2016.3

  A phenotypic screening of thienodiazepines derived from a hit compound found through a binding assay targeting co-stimulatory molecules on T cells and antigen presenting cells successfully led to the discovery of a thienotriazolodiazepine compound (7f) possessing potent immunosuppressive activity. A chemical biology approach has succeeded in revealing that 7f is a first inhibitor of epigenetic bromodomain-containing proteins. 7f is expected to become an anti-cancer agent as well as an immunosuppressive agent. (C) 2016 Elsevier Ltd. All rights reserved.