6-{3-[2-phenethyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-benzimidazole-5-carbonyl]-ureido}-hexanoic acid hydroxyamide | 1235976-34-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 6-{3-[2-phenethyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-benzimidazole-5-carbonyl]-ureido}-hexanoic acid hydroxyamide
• 英文别名: N-[[6-(hydroxyamino)-6-oxohexyl]carbamoyl]-2-(2-phenylethyl)-1-(2-pyrrolidin-1-ylethyl)benzimidazole-5-carboxamide
• CAS: 1235976-34-7
• 化学式: C₂₉H₃₈N₆O₄
• 分子量: 534.659
• InChiKey: FLEMUVTXATYOIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-{3-[2-phenethyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-benzimidazole-5-carbonyl]-ureido}-hexanoic acid hydroxyamide 、 三氟乙酸 以 水 、 乙腈 为溶剂， 以78.3 mg的产率得到6-{3-[2-phenethyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-benzimidazole-5-carbonyl]-ureido}-hexanoic acid hydroxyamide bistrifluoroacetic acid
  参考文献：
  名称：

  Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity

  摘要：

  Thirty-six novel acylurea connected straight chain hydroxamates were designed and synthesized. Structure-activity relationships (SAR) were established for the length of linear chain linker and substitutions on the benzoylurea group. Compounds 5g, 5i, 5n, and 19 showed 10-20-fold enhanced HDAC1 potency compared to SAHA. In general, the cellular potency pIC(50) (COLO205) correlates with enzymatic potency pIC50 ( HDAC1). Compound 5b (SB207), a structurally simple and close analogue to SAHA, is more potent against HDAC1 and HDAC6 compared to the latter. As a representative example of this series, good in vitro enzymatic and cellular potency plus an excellent pharmacokinetic profile has translated into better efficacy than SAHA in both prostate cancer (PC3) and colon cancer (HCT116) xenograft models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.041
• 作为产物：
  描述：

  在 盐酸羟胺 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 6-{3-[2-phenethyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-benzimidazole-5-carbonyl]-ureido}-hexanoic acid hydroxyamide
  参考文献：
  名称：

  Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity

  摘要：

  Thirty-six novel acylurea connected straight chain hydroxamates were designed and synthesized. Structure-activity relationships (SAR) were established for the length of linear chain linker and substitutions on the benzoylurea group. Compounds 5g, 5i, 5n, and 19 showed 10-20-fold enhanced HDAC1 potency compared to SAHA. In general, the cellular potency pIC(50) (COLO205) correlates with enzymatic potency pIC50 ( HDAC1). Compound 5b (SB207), a structurally simple and close analogue to SAHA, is more potent against HDAC1 and HDAC6 compared to the latter. As a representative example of this series, good in vitro enzymatic and cellular potency plus an excellent pharmacokinetic profile has translated into better efficacy than SAHA in both prostate cancer (PC3) and colon cancer (HCT116) xenograft models. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.041