methyl (3-methylphenethyl)carbamate | 1216826-48-0

• 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: methyl (3-methylphenethyl)carbamate
• 英文别名: methyl N-[2-(3-methylphenyl)ethyl]carbamate
• CAS: 1216826-48-0
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: AEXUSMQJHIXUJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl (3-methylphenethyl)carbamate 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.17h， 生成 6-(6-methyl-3,4-dihydro-1H-isoquinolin-2-yl)-N-(6-methylpyridin-2-yl)nicotinamide
  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：

  1-methyl-3-(2-nitrovinyl)benzene 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 methyl (3-methylphenethyl)carbamate
  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

• Activation of Electrophilicity of Stable Y-Delocalized Carbamate Cations in Intramolecular Aromatic Substitution Reaction: Evidence for Formation of Diprotonated Carbamates Leading to Generation of Isocyanates
  作者：Hiroaki Kurouchi、Kyoko Kawamoto、Hiromichi Sugimoto、Satoshi Nakamura、Yuko Otani、Tomohiko Ohwada

  DOI：10.1021/jo3020566

  日期：2012.10.19

  idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped

  尽管具有三个杂原子的阳离子（例如单质子化的胍和尿素）通过Y形共轭而稳定，并且此类Y缀合的阳离子具有足够的碱性，可以在强酸介质中进一步质子化（或原溶剂化）为离子，但只有O-单质子化的物质具有即使在魔幻酸中也能检测到氨基甲酸酯。我们发现，三氟甲磺酸催化的芳基氨基甲酸酯的环化反应以高收率提供二氢异喹诺酮。在强酸中，氨基甲酸甲酯完全被O-单质子化，即使在加热下，这些单阳离子也不会发生环化。但是，随着反应介质酸度的进一步增加，苯乙基氨基甲酸甲酯的环化反应开始作为一级反应进行，速率和酸度之间呈线性关系。小号⧧被认为是类似其他A的AC 1反应。这些结果强烈支持以下想法：O质子化的氨基甲酸酯进一步质子化参与环化反应，但是这些药物的浓度非常低，这表明决定速率的步骤是甲醇从双质子化的氨基甲酸酯中解离生成质子化的异氰酸酯。与芳环反应。因此，与其他Y形单阳离子形成鲜明对比的是，O质子化的氨基甲酸酯是弱碱。
• PYRIMIDINE-2,4-DIAMINE DERIVATIVE AND ANTICANCER PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US20170145007A1

  公开（公告）日：2017-05-25

  The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.

  本发明涉及一种嘧啶-2,4-二胺衍生物或其药学上可接受的盐，以及包含该衍生物作为有效成分的用于预防或治疗癌症的药物组合物。根据本发明的化合物具有良好的抑制间变性淋巴瘤激酶（ALK）活性的效果，从而能够增强对含有间变性淋巴瘤激酶（ALK）融合蛋白（如EML4-ALK、NPM-ALK等）的癌细胞的治疗效果，并有望有效抑制癌症的复发。因此，该化合物可有效地用于预防或治疗癌症的药物组合物中。
• Organocatalyzed Birch Reduction Driven by Visible Light
  作者：Justin P. Cole、Dian-Feng Chen、Max Kudisch、Ryan M. Pearson、Chern-Hooi Lim、Garret M. Miyake

  DOI：10.1021/jacs.0c05899

  日期：2020.8.5

  The Birch reduction is a powerful synthetic methodology that uses solvated electrons to convert inert arenes to 1,4-cyclohexadienes-valuable intermediates for building molecular complexity. Birch reductions traditionally employ alkali metals dissolved in ammonia to produce a solvated electrons for the reduction of unactivated arenes such as benzene (Ered < -3.42 V vs. SCE). Photoredox catalysts have

  Birch 还原是一种强大的合成方法，它使用溶剂化电子将惰性芳烃转化为 1,4-环己二烯有价值的中间体，以构建分子复杂性。桦木还原传统上使用溶解在氨中的碱金属来产生溶剂化电子，用于还原未活化的芳烃，例如苯（Ered < -3.42 V vs. SCE）。光氧化还原催化剂在高度还原应用中越来越受欢迎，但没有报道显示出足以减少苯的还原潜力。在这里，我们引入苯并苝酰亚胺作为新型有机光氧化还原催化剂，用于在环境温度下进行桦木还原，并由市售 LED 的可见光驱动。使用低催化剂负载量（<1 摩尔百分比），在完全无金属的反应中，苯和其他官能化芳烃以中等至良好的产率选择性地转化为 1,4-环己二烯。机理研究表明，这种前所未有的可见光诱导反应是通过有机光氧化还原催化剂利用两个可见光光子的能量影响单个高能化学转化的能力实现的。
• 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.