(E)-3-(5-{(E)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid tert-butyl ester | 952281-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (E)-3-(5-{(E)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid tert-butyl ester
• 英文别名: tert-butyl (E)-3-[5-[(E)-3-[4-(4-methylpiperazin-1-yl)phenyl]-3-oxoprop-1-enyl]pyridin-2-yl]prop-2-enoate
• CAS: 952281-69-5
• 化学式: C₂₆H₃₁N₃O₃
• 分子量: 433.55
• InChiKey: YYAVHGKFIDNKEX-BIVKKUJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(5-{(E)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid tert-butyl ester 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 5.0h， 以100%的产率得到(E)-3-(5-{(E)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid bis-trifluoroacetate
  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：

  (E)-3-(5-formylpyridin-2-yl)acrylic acid tert-butyl ester 、 1-[4-(4-甲基哌嗪)苯基]-1-苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以45%的产率得到(E)-3-(5-{(E)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid tert-butyl ester
  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。
• Class of histone deacetylase inhibitors
  申请人：DAC S.R.L.

  公开号：US08242175B2

  公开（公告）日：2012-08-14

  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.

  新的组蛋白去乙酰化酶抑制剂，其通式为（I），其中：Q为键，CH2，CH—NR3R4，NR5或氧，X为CH或氮，Y为键，CH2，氧或NR6，Z为CH或氮，R1，R2独立地为氢，卤素，C1-C6烷基或C1-C6卤代烷基，R11，R12独立地为氢或C1-C6烷基，而R3，R4，R5和R6如规范中进一步定义。
• 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