dibenzyl 1,4-dihydro-2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylate | 80611-86-5

• 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: dibenzyl 1,4-dihydro-2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylate
• 英文别名: 2,6-Dimethyl-4-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dibenzyl ester；dibenzyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 80611-86-5
• 化学式: C₂₉H₂₇NO₄
• mdl: MFCD02667571
• 分子量: 453.538
• InChiKey: UYRYZSBDOFVCML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dibenzyl 1,4-dihydro-2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylate 在 1,3-二溴-5,5-二甲基海因 、 C₄₄H₂₉O₄P 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以63%的产率得到dibenzyl (S)-2-(bromomethyl)-6-methyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  手性磷酸催化 C(sp3)-H 溴化对 1,4-二氢吡啶的对映选择性去对称化

  摘要：

  容易获得的对称 1,4-二氢吡啶 (1,4-DHP) 被用作底物以获得药物中经常含有的手性 Hantzsch 型 1,4-DHP。惰性 C-H 键被转化为通用的 C-Br 键，从而能够通过亲核取代高效地修饰手性 1,4-DHP 衍生物。此外，轴向手性 4-芳基吡啶可通过中心到轴向手性转换获得。

  DOI：

  10.1002/anie.202201418
• 作为产物：
  描述：

  乙酰丙酮苄酯 、 苯甲醛 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 dibenzyl 1,4-dihydro-2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors

  摘要：

  BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30 mu M, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors.

  DOI：

  10.1016/j.ejmech.2010.02.046

文献信息

• Metal free biomimetic deaminative direct C–C coupling of unprotected primary amines with active methylene compounds
  作者：Santanu Ghosh、Chandan K. Jana

  DOI：10.1039/c9ob02163a

  日期：——

  unprecedented direct C–C coupling reaction of unprotected primary amines with active methylene compounds is reported. The reaction involves a biomimetic deamination of amines which was achieved under conditions free of metallic reagents and strong oxidizing agents. A wide range of primary amines was reacted with different active methylene compounds to provide structurally diverse trisubstituted alkenes and

  据报道，未保护的伯胺与活性亚甲基化合物进行了前所未有的直接CC偶联反应。该反应包括在没有金属试剂和强氧化剂的条件下实现的胺的仿生脱氨基。使各种伯胺与不同的活性亚甲基化合物反应，以提供结构上不同的三取代烯烃和二氢吡啶。动力学研究揭示了10.1 kcal mol -1的活化势垒，用于反应关键中间体的转化。
• US4567268A
  申请人：——

  公开号：US4567268A

  公开（公告）日：1986-01-28
• Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors
  作者：Soo-Jeong Choi、Joong-Heui Cho、Isak Im、So-Deok Lee、Ji-Yeon Jang、Yu-Min Oh、Yong-Keun Jung、Eun-Seok Jeon、Yong-Chul Kim

  DOI：10.1016/j.ejmech.2010.02.046

  日期：2010.6

  BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30 mu M, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors.
• Chiral Phosphoric Acid Catalyzed Enantioselective Desymmetrization of 1,4‐Dihydropyridines by C(sp ³ )−H Bromination
  作者：Min Han、Shi‐qi Zhang、Xin Cui、Qi‐wei Wang、Guang‐xun Li、Zhuo Tang

  DOI：10.1002/anie.202201418

  日期：2022.5.23

  used as substrates to obtain chiral Hantzsch-type 1,4-DHPs, which are frequently contained in pharmaceuticals. The inert C−H bond was converted into a versatile C−Br bond, which enabled the modification of the chiral 1,4-DHP derivatives with high efficiency by nucleophilic substitution. Furthermore, axially chiral 4-aryl pyridines were accessible by central-to-axial chirality conversion.

  容易获得的对称 1,4-二氢吡啶 (1,4-DHP) 被用作底物以获得药物中经常含有的手性 Hantzsch 型 1,4-DHP。惰性 C-H 键被转化为通用的 C-Br 键，从而能够通过亲核取代高效地修饰手性 1,4-DHP 衍生物。此外，轴向手性 4-芳基吡啶可通过中心到轴向手性转换获得。