[(S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl]acetic acid ethyl ester | 916490-11-4

• 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-chlorophenyl)-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-chlorophenyl)-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-chlorophenyl)-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: 916490-11-4
• 化学式: C₂₁H₂₁ClN₄O₂S
• 分子量: 428.942
• InChiKey: DLPVUDJPMYIRDC-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 在 bis-triphenylphosphine-palladium(II) chloride 、 双(三环己基膦)二氯化钯 、 potassium acetate 、 sodium carbonate 、 caesium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 丁酮 为溶剂， 反应 11.0h， 生成 {(S)-4-[4'-(3-aminopropoxy)-3'-cyanobiphenyl-4-yl]-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
• 作为产物：
  描述：

  (+)-JQ1羧酸 在 硫酸 作用下， 以 乙醇 为溶剂， 以45 g的产率得到[(S)-4-(4-chlorophenyl)-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：

  ＢＲＤ４蛋白質分解誘導剤を含む医薬

  摘要：

  【課題】ＢＲＤ４蛋白質分解誘導作用に優れる化合物を含み、がんの治療剤として有用な医薬組成物を提供すること。【解決手段】下記式（Ｉ）で表される化合物又はその医薬的に許容される塩を含む医薬組成物。 JPEG 2023024381000448.jpg 58 130 ｛式中、各記号は明細書中で定義した通りである。｝【選択図】なし

  公开号：

  JP2023024381A

文献信息

• THIENOTRIAZOLODIAZEPINE COMPOUND AND MEDICINAL USE THEREOF
  申请人：Adachi Kunitomo

  公开号：US20100041643A1

  公开（公告）日：2010-02-18

  [Solving means] A thienotriazolodiazepine compound of the following formula (I) a pharmaceutical agent containing the compound as an active ingredient, and a production intermediate and a production method of the thienotriazolodiazepine compound. [Effect]Since this compound has an inhibitory action on costimulatory signal from CD28 on T cell, it is useful for the prophylaxis or suppression of rejection reaction in transplantation of organ or bone marrow and the like, and the prophylaxis or treatment of autoimmune diseases or allergic diseases.

  【解决方法】以下式(I)的噻唑三唑二氮杂环化合物，以其为活性成分的药物制剂，以及噻唑三唑二氮杂环化合物的生产中间体和生产方法。 【效果】由于该化合物对T细胞上的CD28共刺激信号具有抑制作用，因此它对于预防或抑制器官或骨髓移植等排斥反应，以及预防或治疗自身免疫性疾病或过敏疾病非常有用。
• SULFONAMIDE OR SULFINAMIDE COMPOUND HAVING EFFECT OF INDUCING BRD4 PROTEIN DEGRADATION AND PHARMACEUTICAL USE THEREOF
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP4105220A1

  公开（公告）日：2022-12-21

  Provided is a compound or a pharmaceutically acceptable salt thereof which is superior in an action inducing degradation of BRD4 protein and useful as a therapeutic agent for cancer. A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the DESCRIPTION.

  本发明提供了一种化合物或其药学上可接受的盐，该化合物或其药学上可接受的盐在诱导 BRD4 蛋白降解的作用方面具有优势，可用作癌症治疗剂。由下式（I）代表的化合物或其药学上可接受的盐： 其中各符号如说明书中所定义。
• 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
• US8044042B2
  申请人：——

  公开号：US8044042B2

  公开（公告）日：2011-10-25
• 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.