(E)-3-[4-(2-methylaminoethylamino)-3-nitrophenyl]acrylic acid methyl ester | 929018-79-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-[4-(2-methylaminoethylamino)-3-nitrophenyl]acrylic acid methyl ester
• 英文别名: 3-(4-(2-methylaminoethylamino)-3-nitrophenyl)-acrylic acid methyl ester；methyl (E)-3-[4-[2-(methylamino)ethylamino]-3-nitrophenyl]prop-2-enoate
• CAS: 929018-79-1
• 化学式: C₁₃H₁₇N₃O₄
• 分子量: 279.296
• InChiKey: LMQHJAAMPCCITR-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-[4-(2-methylaminoethylamino)-3-nitrophenyl]acrylic acid methyl ester 在 tin(II) chloride dihdyrate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Discovery of (2E)-3-{2-Butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an Orally Active Histone Deacetylase Inhibitor with a Superior Preclinical Profile

  摘要：

  A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC I enzyme and COLO 205 cellular IC50), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC50), and clogP, among others. These parameters were fine-tuned by carefully adjusting the substituents at positions 1 and 2 of the benzimidazole ring. After comprehensive in vitro and in vivo profiling of the selected compounds, SB939 (3) was identified as a preclinical development candidate. 3 is a potent pan-HDAC inhibitor with excellent druglike properties, is highly efficacious in in vivo tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos), and has high and dos-proportional oral exposures and very good ADME, safety, and pharmaceutical properties. When orally dosed to tumor-bearing mice, 3 is enriched in tumor tissue which may contribute to its potent antitumor activity and prolonged duration of action. 3 is currently being tested in phase I and phase II clinical trials.

  DOI：

  10.1021/jm2003552
• 作为产物：
  描述：

  4-氯-3-硝基肉桂酸 在 硫酸 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 (E)-3-[4-(2-methylaminoethylamino)-3-nitrophenyl]acrylic acid methyl ester
  参考文献：
  名称：

  Discovery of (2E)-3-{2-Butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an Orally Active Histone Deacetylase Inhibitor with a Superior Preclinical Profile

  摘要：

  A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC I enzyme and COLO 205 cellular IC50), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC50), and clogP, among others. These parameters were fine-tuned by carefully adjusting the substituents at positions 1 and 2 of the benzimidazole ring. After comprehensive in vitro and in vivo profiling of the selected compounds, SB939 (3) was identified as a preclinical development candidate. 3 is a potent pan-HDAC inhibitor with excellent druglike properties, is highly efficacious in in vivo tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos), and has high and dos-proportional oral exposures and very good ADME, safety, and pharmaceutical properties. When orally dosed to tumor-bearing mice, 3 is enriched in tumor tissue which may contribute to its potent antitumor activity and prolonged duration of action. 3 is currently being tested in phase I and phase II clinical trials.

  DOI：

  10.1021/jm2003552

文献信息

• Heterocyclic Compounds
  申请人：Chen Dizhong

  公开号：US20090048300A1

  公开（公告）日：2009-02-19

  The present invention relates to compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to heterocyclic compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.

  本发明涉及一种组合物，该组合物是组蛋白去乙酰化酶的抑制剂。更具体地，本发明涉及杂环化合物及其制备方法。这些化合物可能作为药物用于治疗增殖性疾病以及涉及、与或与组蛋白去乙酰化酶（HDAC）活性有关的其他疾病。
• COMBINATION OF BENZIMIDAZOLE ANTI-CANCER AGENT AND A SECOND ANTI-CANCER AGENT
  申请人：Goh Kay Lin

  公开号：US20100098691A1

  公开（公告）日：2010-04-22

  The present invention relates to a pharmaceutical composition for the treatment of cancer as well as methods of treatment of cancer that are based on the finding that certain benzimidazole based anti-cancer agents can be used in combination with a second anti-cancer agent to achieve desirable therapeutic outcomes. More specifically the present invention relates to a pharmaceutical composition including a benzimidazole based anti-cancer agent and a second anti-cancer agent. The invention also relates to methods of treatment of cancer including administration of a benzimidazole based anti-cancer agent and a second anti-cancer agent to a patient in need thereof.

  本发明涉及一种用于癌症治疗的制药组合物，以及基于发现某些基于苯并咪唑的抗癌药物可以与第二种抗癌药物结合使用以达到理想的治疗效果的癌症治疗方法。更具体地，本发明涉及一种包括基于苯并咪唑的抗癌药物和第二种抗癌药物的制药组合物。本发明还涉及癌症治疗方法，包括向需要治疗的患者施用基于苯并咪唑的抗癌药物和第二种抗癌药物。
• HETEROCYCLIC COMPOUNDS
  申请人：S*BIO Pte Ltd

  公开号：EP1937650A1

  公开（公告）日：2008-07-02
• US8143282B2
  申请人：——

  公开号：US8143282B2

  公开（公告）日：2012-03-27
• [EN] HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLIQUES
  申请人：S BIO PTE LTD

  公开号：WO2007030080A1

  公开（公告）日：2007-03-15

  [EN] The present invention relates to compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to heterocyclic compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase (HDAC) activities.
  [FR] La présente invention concerne des composés qui sont des inhibiteurs d'histone désacétylase. Plus particulièrement, la présente invention concerne des composés hétérocycliques et leurs procédés de préparation. Ces composés peuvent être utiles en tant que médicaments pour le traitement de troubles prolifératifs ainsi que d'autres maladies impliquant, concernant des enzymes ayant des activités histone désacétylase (HDAC) ou associés à celles-ci.