3-(2-acetyl-8-chloro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)propanoic acid | 1512863-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(2-acetyl-8-chloro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)propanoic acid
• 英文别名: 3-(2-acetyl-8-chloro-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)propanoic acid
• CAS: 1512863-32-9
• 化学式: C₁₆H₁₇ClN₂O₃
• 分子量: 320.776
• InChiKey: KENTVNFHBUBUAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-acetyl-8-chloro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)propanoic acid 、 甲胺 在 N,N'-羰基二咪唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 4.0h， 以46%的产率得到3-(2-acetyl-8-chloro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)-N-methylpropanamide
  参考文献：
  名称：

  Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design against the BAZ2B Bromodomain

  摘要：

  Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fragments into a novel series of low-micromolar inhibitors. Our results provide attractive leads for development of BAZ2B chemical probes and indicate the whole family may be tractable.

  DOI：

  10.1021/jm401582c
• 作为产物：
  描述：

  N-acetylpiperidin-4-one hydrochloride 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 35.0h， 生成 3-(2-acetyl-8-chloro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)propanoic acid
  参考文献：
  名称：

  Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design against the BAZ2B Bromodomain

  摘要：

  Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fragments into a novel series of low-micromolar inhibitors. Our results provide attractive leads for development of BAZ2B chemical probes and indicate the whole family may be tractable.

  DOI：

  10.1021/jm401582c

文献信息

• Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design against the BAZ2B Bromodomain
  作者：Fleur M. Ferguson、Oleg Fedorov、Apirat Chaikuad、Martin Philpott、Joao R. C. Muniz、Ildiko Felletar、Frank von Delft、Tom Heightman、Stefan Knapp、Chris Abell、Alessio Ciulli

  DOI：10.1021/jm401582c

  日期：2013.12.27

  Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fragments into a novel series of low-micromolar inhibitors. Our results provide attractive leads for development of BAZ2B chemical probes and indicate the whole family may be tractable.