3-[2-butyl-5-(2-methoxycarbonylvinyl)benzimidazol-1-yl]pyrrolidine-1-carboxylic acid tert-butyl ester | 929019-04-5

• 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: 3-[2-butyl-5-(2-methoxycarbonylvinyl)benzimidazol-1-yl]pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 3-[2-butyl-5-[(E)-3-methoxy-3-oxoprop-1-enyl]benzimidazol-1-yl]pyrrolidine-1-carboxylate
• CAS: 929019-04-5
• 化学式: C₂₄H₃₃N₃O₄
• 分子量: 427.544
• InChiKey: OQNJNACLRZSDHF-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[2-butyl-5-(2-methoxycarbonylvinyl)benzimidazol-1-yl]pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 methyl (E)-3-(2-butyl-1-(pyrrolidin-3-yl)-1H-benzo[d]imidazol-5-yl)acrylate hydrochloride
  参考文献：
  名称：

  WO2007/30080

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl 3-[4-[(E)-3-methoxy-3-oxoprop-1-enyl]-2-nitroanilino]pyrrolidine-1-carboxylate 在 tin(ll) chloride 、 sodium carbonate 作用下， 以 甲醇 、 溶剂黄146 、 水 、 乙酸乙酯 为溶剂， 反应 25.0h， 以44%的产率得到3-[2-butyl-5-(2-methoxycarbonylvinyl)benzimidazol-1-yl]pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2007/30080

  摘要：

  公开号：

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。
• US8143282B2
  申请人：——

  公开号：US8143282B2

  公开（公告）日：2012-03-27
• Discovery of (2<i>E</i>)-3-{2-Butyl-1-[2-(diethylamino)ethyl]-1<i>H</i>-benzimidazol-5-yl}-<i>N</i>-hydroxyacrylamide (SB939), an Orally Active Histone Deacetylase Inhibitor with a Superior Preclinical Profile
  作者：Haishan Wang、Niefang Yu、Dizhong Chen、Ken Chi Lik Lee、Pek Ling Lye、Joyce Wei Wei Chang、Weiping Deng、Melvin Chi Yeh Ng、Ting Lu、Mui Ling Khoo、Anders Poulsen、Kanda Sangthongpitag、Xiaofeng Wu、Changyong Hu、Kee Chuan Goh、Xukun Wang、Lijuan Fang、Kay Lin Goh、Hwee Hoon Khng、Siok Kun Goh、Pauline Yeo、Xin Liu、Zahid Bonday、Jeanette M. Wood、Brian W. Dymock、Ethirajulu Kantharaj、Eric T. Sun

  DOI：10.1021/jm2003552

  日期：2011.7.14

  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.
• WO2007/30080
  申请人：——

  公开号：——

  公开（公告）日：——