(E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid hydrochloride | 1204230-72-7

• 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-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid hydrochloride
• 英文别名: (E)-3-[4-[(E)-3-[2-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid;hydrochloride
• CAS: 1204230-72-7
• 化学式: C₂₃H₂₄N₂O₃*ClH
• 分子量: 412.916
• InChiKey: JXVALTDHDKYQQX-BSENIABMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.85
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O-(四氢-2H-吡喃-2-基)羟基胺 、 (E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid hydrochloride 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 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  WO2007/113249

  摘要：

  公开号：
• 作为产物：
  描述：

  (E)-3-[4-[(E)-3-[2-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]phenyl]prop-2-enoic acid 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以930 mg的产率得到(E)-3-(4-{(E)-3-[2-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid 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

文献信息

• CLASS OF HISTONE DEACETYLASE INHIBITORS
  申请人：Mai Antonello

  公开号：US20100113438A1

  公开（公告）日：2010-05-06

  New histone deacetylase inhibitors according to the general formula (I) wherein: Q is a bond, CH 2 , CH—NR 3 R 4 , NR 5 or oxygen, X is CH or nitrogen, Y is a bond, CH 2 , oxygen or NR 6 , Z is CH or nitrogen, R 1 , R 2 are, independently, hydrogen, halogen, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, R 11 , R 12 are, independently, hydrogen or C 1 -C 6 alkyl, and R 3 , R 4 , R 5 and R 6 are as further defined in the specification.

  新的组蛋白去乙酰化酶抑制剂具有以下通式（I）：其中：Q是键，CH2，CH—NR3R4，NR5或氧，X是CH或氮，Y是键，CH2，氧或NR6，Z是CH或氮，R1，R2分别是氢，卤素，C1-C6烷基或C1-C6卤代烷基，R11，R12分别是氢或C1-C6烷基，R3，R4，R5和R6如规范中所进一步定义。
• WO2007/113249
  申请人：——

  公开号：——

  公开（公告）日：——
• 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：EP2049508B1

  公开（公告）日：2010-06-09
• US8242175B2
  申请人：——

  公开号：US8242175B2

  公开（公告）日：2012-08-14
• [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