trans-2-Ethoxymethylen-3-ethoxy-propionsaeure-ethylester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯酯类
• 英文名称: trans-2-Ethoxymethylen-3-ethoxy-propionsaeure-ethylester
• 英文别名: Ethyl 3-ethoxy-2-(ethoxymethyl)prop-2-enoate；ethyl 3-ethoxy-2-(ethoxymethyl)prop-2-enoate
• 化学式: C₁₀H₁₈O₄
• 分子量: 202.251
• InChiKey: IRRQGVYKABYQGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-2-Ethoxymethylen-3-ethoxy-propionsaeure-ethylester 在 溴 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 2-氯嘧啶-5-羧酸乙酯
  参考文献：
  名称：

  Design and synthesis of novel androgen receptor antagonists via molecular modeling

  摘要：

  Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50 = 0.35 mu M) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.047
• 作为产物：
  描述：

  3-乙氧基丙酸乙酯 、 甲酸乙酯 在 sodium ethanolate 、 硫酸二甲酯 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以100%的产率得到trans-2-Ethoxymethylen-3-ethoxy-propionsaeure-ethylester
  参考文献：
  名称：

  Design and synthesis of novel androgen receptor antagonists via molecular modeling

  摘要：

  Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50 = 0.35 mu M) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.047

文献信息

• Studies on the Pyrimidine Derivatives and the Related Compounds. XXXVIII. Investigation on 2-Alkoxy-methylene-3-ethoxypropionitrile and Ethyl 2-Alkoxymethylene-3-ethoxypropionate
  作者：Akira Takamizawa、Kentaro Hirai、Shinzaburo Sumimoto

  DOI：10.1248/cpb.14.238

  日期：——

  cis-and trans-2-Methoxymethylene-3-ethoxypropiontirile and 2-ethoxymethylene compounds are successfully separated and their structures were determined. Corresponding ester derivatives were not able to separate, however, the ratio of cis/transformation was made clear by elimination of ethyl alcohol from corresponding acetal compounds.

  反式和顺式-2-甲氧亚甲基-3-乙氧基丙腈和2-乙氧亚甲基化合物被成功分离，并确定了它们的结构。然而，相应的酯衍生物未能分开，但通过从相应的缩醛化合物中除去乙醇，明确了顺反异构体比例。
• WO2024159162A1
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and synthesis of novel androgen receptor antagonists via molecular modeling
  作者：Chao Zhao、You Hee Choi、Daulat Bikram Khadka、Yifeng Jin、Kwang-Youl Lee、Won-Jea Cho

  DOI：10.1016/j.bmc.2015.12.047

  日期：2016.2

  Several androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50 = 0.35 mu M) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biological results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied molecular modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chemical modifications. (c) 2015 Elsevier Ltd. All rights reserved.