methyl 6-{[2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)acetyl]amino}hexanoate | 1147683-08-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: methyl 6-{[2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)acetyl]amino}hexanoate
• 英文别名: Methyl 6-[[2-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)acetyl]amino]hexanoate
• CAS: 1147683-08-6
• 化学式: C₂₄H₂₇NO₃
• 分子量: 377.483
• InChiKey: NOBJOTTUNMKUBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6-{[2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)acetyl]amino}hexanoate 在 盐酸羟胺 、 sodium methylate 作用下， 以 甲醇 为溶剂， 以64%的产率得到6-{[2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)acetyl]amino}-N-hydroxyhexanamide
  参考文献：
  名称：

  Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR

  摘要：

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.020
• 作为产物：
  描述：

  2-(10,11-dihydro-5H-dibenzocyclohepten-5-ylidene)acetic acid 、 6-氨基己酸甲酯 盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以83%的产率得到methyl 6-{[2-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)acetyl]amino}hexanoate
  参考文献：
  名称：

  TRICYCLIC DERIVATIVES AS POTENT AND SELECTIVE HISTONE DEACETYLASE INHIBITORS

  摘要：

  本发明涉及某些三环衍生物，能够抑制组蛋白去乙酰化酶。因此，本发明的化合物在治疗与异常组蛋白去乙酰化酶活性相关的疾病方面具有用途。还公开了包含这些化合物的药物组合物、利用包含这些化合物的药物组合物治疗疾病的方法，以及制备这些化合物的方法。

  公开号：

  US20090292001A1

文献信息

• TRICYCLIC DERIVATIVES AS POTENT AND SELECTIVE HISTONE DEACETYLASE INHIBITORS
  申请人：LU Xian-Ping

  公开号：US20090292001A1

  公开（公告）日：2009-11-26

  The present invention relates to certain tricyclic derivatives which are capable of inhibiting histone deacetylases. The compounds of this invention are therefore useful in treating diseases associated with abnormal histone deacetylase activities. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing these compounds are also disclosed.

  本发明涉及某些三环衍生物，能够抑制组蛋白去乙酰化酶。因此，本发明的化合物在治疗与异常组蛋白去乙酰化酶活性相关的疾病方面具有用途。还公开了包含这些化合物的药物组合物、利用包含这些化合物的药物组合物治疗疾病的方法，以及制备这些化合物的方法。
• US8178577B2
  申请人：——

  公开号：US8178577B2

  公开（公告）日：2012-05-15
• Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR
  作者：Victor Andrianov、Vija Gailite、Daina Lola、Einars Loza、Valentina Semenikhina、Ivars Kalvinsh、Paul Finn、Kamille Dumong Petersen、James W.A. Ritchie、Nagma Khan

  DOI：10.1016/j.ejmech.2008.06.020

  日期：2009.3

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.