(E)-3-[4-[(E)-3-[2-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid | 952391-10-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-[4-[(E)-3-[2-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid
• CAS: 952391-10-5
• 化学式: C₂₄H₂₆N₂O₃
• 分子量: 390.482
• InChiKey: OOLAUMAWNBMNMH-DCIPZJNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-[4-[(E)-3-[2-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以350 mg的产率得到(E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid bis-hydrochloride
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2-ylacrylamides as Novel Histone Deacetylase Inhibitors

  摘要：

  The historic deacetylases (HDACs) are able to regulate gene expression, and historic deacetylase inhibitors (HDACi) emerged as a new class of agents in the treatment of cancer as well as other human disorders such as neurodegenerative diseases. In the present investigation, we report on the synthesis and biological evaluation of compounds derived from the expansion of a HDAC inhibitor scaffold having N-hydroxy-3-phenyl-2-propenamide and N-hydroxy-3-(pyridin-2-yl)-2-propenamide as core structures and containing a phenyloxopropenyl moiety, either unsubstituted or substituted by a 4-methylpiperazin-1-yl or 4-methylpiperazin-1-ylmethyl group. The compounds were evaluated for their ability to inhibit nuclear HDACs, as well as for their in vitro antiproliferative activity. Moreover, their metabolic stability in microsomes and aqueous Solubility were studied and selected compounds were further characterized by in vivo pharmacokinetic experiments. These compounds showed a remarkable stability in vivo, compared to hydroxamic acid HDAC inhibitors that have already entered clinical trials. The representative compound 30b showed in vivo antitumor activity in a human colon carcinoma xenograft model.

  DOI：

  10.1021/jm901502p
• 作为产物：
  描述：

  1-[2-(4-methylpiperazin-1-ylmethyl)phenyl]ethanone 、 3-(4-甲酰基苯基)丙-2-烯酸 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 (E)-3-[4-[(E)-3-[2-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2-ylacrylamides as Novel Histone Deacetylase Inhibitors

  摘要：

  The historic deacetylases (HDACs) are able to regulate gene expression, and historic deacetylase inhibitors (HDACi) emerged as a new class of agents in the treatment of cancer as well as other human disorders such as neurodegenerative diseases. In the present investigation, we report on the synthesis and biological evaluation of compounds derived from the expansion of a HDAC inhibitor scaffold having N-hydroxy-3-phenyl-2-propenamide and N-hydroxy-3-(pyridin-2-yl)-2-propenamide as core structures and containing a phenyloxopropenyl moiety, either unsubstituted or substituted by a 4-methylpiperazin-1-yl or 4-methylpiperazin-1-ylmethyl group. The compounds were evaluated for their ability to inhibit nuclear HDACs, as well as for their in vitro antiproliferative activity. Moreover, their metabolic stability in microsomes and aqueous Solubility were studied and selected compounds were further characterized by in vivo pharmacokinetic experiments. These compounds showed a remarkable stability in vivo, compared to hydroxamic acid HDAC inhibitors that have already entered clinical trials. The representative compound 30b showed in vivo antitumor activity in a human colon carcinoma xenograft model.

  DOI：

  10.1021/jm901502p

文献信息

• N-HYDROXY-3-(4-{3-PHENYL-3-OXO-PROPENYL}-PHENYL)-ACRYLAMIDE DERIVATIVES AND RELATED COMPOUNDS AS HISTONE DEACETYLASE INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：DAC S.r.l.

  公开号：EP2049508A2

  公开（公告）日：2009-04-22
• [EN] A NEW CLASS OF HISTONE DEACETYLASE INHIBITORS<br/>[FR] NOUVELLE CLASSE D'INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：DAC SRL

  公开号：WO2007113249A2

  公开（公告）日：2007-10-11

  [EN] New histone deacetylase inhibitors according to the general formula (I) wherein: Q is a bond, CH₂, CH-NR³R⁴, NR⁵ or oxygen, X is CH or nitrogen, Y is a bond, CH₂, oxygen or NR⁶, Z is CH or nitrogen, R¹, R² are, independently, hydrogen, halogen, C₁-C₆ alkyl or C₁-C₆ haloalkyl, R¹¹, R¹² are, independently, hydrogen or C₁-C₆ alkyl, and R³, R⁴, R⁵ and R⁶ are as further defined in the specification.
  [FR] La présente invention concerne de nouveaux inhibiteurs de l'histone désacétylase de formule générale (I) dans laquelle : Q représente une liaison, un groupe CH₂, un groupe CH-NR³R⁴, un groupe NR⁵ ou un atome d'O, X représente un groupe CH ou un atome de N, Y représente une liaison, un groupe CH₂, un atome d'O ou un groupe NR⁶, Z représente un groupe CH ou un atome de N, R¹ et R² _représe