hexahydro-2-(4-chlorophenyl)-imidazo[1,5-a]pyrazin-3-one | 1002404-56-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: hexahydro-2-(4-chlorophenyl)-imidazo[1,5-a]pyrazin-3-one
• 英文别名: 2-(4-Chlorophenyl)-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyrazin-3-one
• CAS: 1002404-56-9
• 化学式: C₁₂H₁₄ClN₃O
• 分子量: 251.716
• InChiKey: VYVLHRLCGPTAEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  hexahydro-2-(4-chlorophenyl)-imidazo[1,5-a]pyrazin-3-one 、 Boc-(R)-3-氨基-4-(2,4,5-三氟苯基)丁酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以75%的产率得到tert-butyl [(1R)-3-[2-(4-chlorophenyl)-hexahydro-3-oxoimidazo[1,5-a]pyrazin-7(8H)-yl]-3-oxo-1-(2,4,5-trifluorobenzyl)propyl]carbamate
  参考文献：
  名称：

  Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors

  摘要：

  A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC50 = 78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.08.002
• 作为产物：
  描述：

  2-(羟甲基)-1,4-哌嗪二羧酸二叔丁酯 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 偶氮二甲酸二异丙酯 、 sodium hydride 、 三苯基膦 、 甲胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 反应 30.0h， 生成 hexahydro-2-(4-chlorophenyl)-imidazo[1,5-a]pyrazin-3-one
  参考文献：
  名称：

  新型2-取代咪唑并吡嗪酮衍生物的便捷合成

  摘要：

  摘要 以市售的哌嗪-2-羧酸为原料，制备了一系列新型的2-芳基和2-苄基取代的咪唑并吡嗪酮。通过简单的 Buchwald-Hartwig 偶联反应获得中间体 5a-g，并研究了催化剂、碱和溶剂对偶联反应的影响。偶联反应的最佳反应条件为PdCl2(dppf)/NaO-t-Bu/甲苯。图形概要

  DOI：

  10.1080/00397911.2010.525774

文献信息

• Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors
  作者：Yanyun Zhu、Shuang Xia、Mingjie Zhu、Weiyin Yi、Jiagao Cheng、Gonghua Song、Zhong Li、Peng Lu

  DOI：10.1016/j.ejmech.2010.08.002

  日期：2010.11

  A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC50 = 78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Convenient Synthesis of Novel 2-Substituted Imidazopyrazinone Derivatives
  作者：Yanyun Zhu、Gonghua Song、Peng Lu、Mingjie Zhu、Yilang Chen

  DOI：10.1080/00397911.2010.525774

  日期：2012.2.15

  Abstract Starting from commercially available piperazine-2-carboxylic acid, a series of novel 2-aryl and 2-benzyl substituted imidazopyrazinone were prepared. The intermediates 5a–g were obtained through facile Buchwald–Hartwig coupling reaction, and the effects of catalyst, base, and solvent on the coupling reaction were investigated. The optimal reaction conditions for the coupling reaction were

  摘要 以市售的哌嗪-2-羧酸为原料，制备了一系列新型的2-芳基和2-苄基取代的咪唑并吡嗪酮。通过简单的 Buchwald-Hartwig 偶联反应获得中间体 5a-g，并研究了催化剂、碱和溶剂对偶联反应的影响。偶联反应的最佳反应条件为PdCl2(dppf)/NaO-t-Bu/甲苯。图形概要