[(1-ethyl-5-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyloxy)-3-methyl-phenyl]-propyl}-1H-pyrrole-2-carbonyl)-methylamino]-acetic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(1-ethyl-5-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyloxy)-3-methyl-phenyl]-propyl}-1H-pyrrole-2-carbonyl)-methylamino]-acetic acid ethyl ester
• 英文别名: Ethyl 2-[[1-ethyl-5-[3-[4-(3-ethyl-3-hydroxypentoxy)-3-methylphenyl]pentan-3-yl]pyrrole-2-carbonyl]-methylamino]acetate；ethyl 2-[[1-ethyl-5-[3-[4-(3-ethyl-3-hydroxypentoxy)-3-methylphenyl]pentan-3-yl]pyrrole-2-carbonyl]-methylamino]acetate
• 化学式: C₃₁H₄₈N₂O₅
• 分子量: 528.733
• InChiKey: HTPSPIQCOHKJBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(1-ethyl-5-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyloxy)-3-methyl-phenyl]-propyl}-1H-pyrrole-2-carbonyl)-methylamino]-acetic acid ethyl ester 在 lithium hydroxide monohydrate 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以77%的产率得到[(1-ethyl-5-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyloxy)-3-methyl-phenyl]-propyl}-1H-pyrrole-2-carbonyl)-methylamino]-acetic acid
  参考文献：
  名称：

  Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents

  摘要：

  The vitamin D (3) receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons with therapeutic potentials in cancer treatment were synthesized. Among them, 11b and 11g were identified as the most effective agents in reducing the viability of four cancer-cell lines, particularly those of breast-cancer cells, with IC50 values in the submicromolar-concentration range. In addition, 11b and 11g possessed VDR-binding affinities and displayed significant partial VDR-agonistic activities determined by dual-luciferase-reporter assays and human-leukemia-cell-line (HL-60)-differentiation assays. Furthermore, 11b and 11g inhibited tumor growth in an orthotopic breast-tumor model via inhibition of cell proliferation and induction of cell apoptosis. More importantly, 11b and 11g exhibited favorable pharmacokinetic behavior in vivo and did not increase serum calcium levels or cause any other apparent side effects. In summary, 11b and 11g act as novel VDR modulators and may be promising candidates for cancer chemotherapy.

  DOI：

  10.1021/acs.jmedchem.8b00106
• 作为产物：
  描述：

  4-羟基-3-甲基苯甲酸 在 4-二甲氨基吡啶 、 硫酸 、 palladium on activated charcoal 、 三氟化硼乙醚 、 碘 、 甲酸铵 、 sodium hydride 、 potassium carbonate 、 magnesium 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 mineral oil 为溶剂， 反应 37.5h， 生成 [(1-ethyl-5-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyloxy)-3-methyl-phenyl]-propyl}-1H-pyrrole-2-carbonyl)-methylamino]-acetic acid ethyl ester
  参考文献：
  名称：

  Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents

  摘要：

  The vitamin D (3) receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons with therapeutic potentials in cancer treatment were synthesized. Among them, 11b and 11g were identified as the most effective agents in reducing the viability of four cancer-cell lines, particularly those of breast-cancer cells, with IC50 values in the submicromolar-concentration range. In addition, 11b and 11g possessed VDR-binding affinities and displayed significant partial VDR-agonistic activities determined by dual-luciferase-reporter assays and human-leukemia-cell-line (HL-60)-differentiation assays. Furthermore, 11b and 11g inhibited tumor growth in an orthotopic breast-tumor model via inhibition of cell proliferation and induction of cell apoptosis. More importantly, 11b and 11g exhibited favorable pharmacokinetic behavior in vivo and did not increase serum calcium levels or cause any other apparent side effects. In summary, 11b and 11g act as novel VDR modulators and may be promising candidates for cancer chemotherapy.

  DOI：

  10.1021/acs.jmedchem.8b00106

文献信息

• Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents
  作者：Meixi Hao、Siyuan Hou、Lingjing Xue、Haoliang Yuan、Lulu Zhu、Cong Wang、Bin Wang、Chunming Tang、Can Zhang

  DOI：10.1021/acs.jmedchem.8b00106

  日期：2018.4.12

  The vitamin D (3) receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons with therapeutic potentials in cancer treatment were synthesized. Among them, 11b and 11g were identified as the most effective agents in reducing the viability of four cancer-cell lines, particularly those of breast-cancer cells, with IC50 values in the submicromolar-concentration range. In addition, 11b and 11g possessed VDR-binding affinities and displayed significant partial VDR-agonistic activities determined by dual-luciferase-reporter assays and human-leukemia-cell-line (HL-60)-differentiation assays. Furthermore, 11b and 11g inhibited tumor growth in an orthotopic breast-tumor model via inhibition of cell proliferation and induction of cell apoptosis. More importantly, 11b and 11g exhibited favorable pharmacokinetic behavior in vivo and did not increase serum calcium levels or cause any other apparent side effects. In summary, 11b and 11g act as novel VDR modulators and may be promising candidates for cancer chemotherapy.