3-[(2,5-dimethylfuran-3-carbonyl)amino]-3-m-tolylpropionic acid

• 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: 3-[(2,5-dimethylfuran-3-carbonyl)amino]-3-m-tolylpropionic acid
• 英文别名: 3-[(2,5-Dimethylfuran-3-carbonyl)amino]-3-(3-methylphenyl)propanoic acid；3-[(2,5-dimethylfuran-3-carbonyl)amino]-3-(3-methylphenyl)propanoic acid
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: PRYMFKVJZPYCDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基-3-间甲苯丙酸 在 氯化亚砜 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-[(2,5-dimethylfuran-3-carbonyl)amino]-3-m-tolylpropionic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)

  摘要：

  All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities.All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 mu M (compared to liarozole (IC50 = 2.45 mu M) and S8 (IC50 = 3.21 mu M)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of beta-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.036

文献信息

• Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)
  作者：Dongmei Zhao、Bin Sun、Jinhong Ren、Fengrong Li、Shuai Song、Xuejiao Lv、Chenzhou Hao、Maosheng Cheng

  DOI：10.1016/j.bmc.2014.11.036

  日期：2015.3

  All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities.All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 mu M (compared to liarozole (IC50 = 2.45 mu M) and S8 (IC50 = 3.21 mu M)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of beta-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development. (C) 2014 Elsevier Ltd. All rights reserved.