N-[[4-[(2-amino-5-thiophen-2-ylphenyl)carbamoyl]phenyl]methyl]-4-methylpiperazine-1-carboxamide | 1364569-91-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[[4-[(2-amino-5-thiophen-2-ylphenyl)carbamoyl]phenyl]methyl]-4-methylpiperazine-1-carboxamide
• CAS: 1364569-91-4
• 化学式: C₂₄H₂₇N₅O₂S
• 分子量: 449.577
• InChiKey: PJFLXGZBIGGCCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-[(叔丁氧羰基氨基)甲基]苯甲酸 在 盐酸 、 草酰氯 、 ammonium acetate 、 三乙胺 、 N,N-二甲基甲酰胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-[[4-[(2-amino-5-thiophen-2-ylphenyl)carbamoyl]phenyl]methyl]-4-methylpiperazine-1-carboxamide
  参考文献：
  名称：

  Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain

  摘要：

  New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80 mg/kg over 16 days, respectively. These values were comparable to the rate (T/C: 51% at 45 mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80 mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.053

文献信息

• Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain
  作者：Yoshiyuki Hirata、Masahiko Hirata、Yasuyuki Kawaratani、Makio Shibano、Masahiko Taniguchi、Masahide Yasuda、Yoshiro Ohmomo、Yasuo Nagaoka、Kimiye Baba、Shinichi Uesato

  DOI：10.1016/j.bmcl.2012.01.053

  日期：2012.3

  New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80 mg/kg over 16 days, respectively. These values were comparable to the rate (T/C: 51% at 45 mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80 mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.