hexahydro-2-methylimidazo[1,5-a]pyrazin-3-one | 1256815-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡嗪类
• 英文名称: hexahydro-2-methylimidazo[1,5-a]pyrazin-3-one
• 英文别名: 2-methyl-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyrazin-3-one
• CAS: 1256815-08-3
• 化学式: C₇H₁₃N₃O
• mdl: MFCD20688117
• 分子量: 155.2
• InChiKey: FNPLZEGCLDXUNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.857
• 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-methylimidazo[1,5-a]pyrazin-3-one 、 (R)-3-(苄氧基氨基)-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30%的产率得到(3R)-3-(benzyloxyamino)-1-[2-methyl-hexahydro-3-oxoimidazo[1,5-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
  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：

  3-氧代六氢咪唑并[1,5-A]吡嗪-7(1H)-羧酸叔丁酯 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 mineral oil 为溶剂， 生成 hexahydro-2-methylimidazo[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

• [EN] COMBINATION THERAPIES WITH SETD2 INHIBITORS<br/>[FR] POLYTHÉRAPIES AVEC DES INHIBITEURS DE SETD2
  申请人：EPIZYME INC

  公开号：WO2022261243A1

  公开（公告）日：2022-12-15

  The present disclosure provides SETD2 protein inhibitors, and methods, uses, compositions, and kits for treating diseases, disorders, or conditions in a subject with a SETD2 protein inhibitor and a Second Therapeutic Agent, wherein the Second Therapeutic Agent comprises one or more BTK inhibitors, one or more anti-CD20 monoclonal antibodies, one or more alkylating agents, one or more topoisomerase II inhibitors, one or more vinca alkaloids, one or more platinum-based drugs, one or more nucleoside anticancer agents, one or more PI3K inhibitors, one or more CDK4/6 inhibitors, one or more CARM1 inhibitors, one or more inhibitors of enzymes of DNA damage repair, one or more SYK inhibitors, or one or more MEK inhibitors, or a combination thereof.

  本公开提供SETD2蛋白抑制剂，以及使用SETD2蛋白抑制剂和第二治疗剂治疗受试者的方法、用途、组合物和试剂盒，其中第二治疗剂包括一种或多种BTK抑制剂、一种或多种抗CD20单克隆抗体、一种或多种烷基化剂、一种或多种拓扑异构酶II抑制剂、一种或多种长春烷类生物碱、一种或多种铂类药物、一种或多种核苷类抗癌药物、一种或多种PI3K抑制剂、一种或多种CDK4/6抑制剂、一种或多种CARM1抑制剂、一种或多种DNA损伤修复酶抑制剂、一种或多种SYK抑制剂或一种或多种MEK抑制剂，或其组合。
• 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