5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile | 89939-60-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile
• 英文别名: 7-hydroxy-5-methylpyrazolo<1,5-a>pyrimidine-3-carbonitrile
• CAS: 89939-60-6
• 化学式: C₈H₆N₄O
• 分子量: 174.162
• InChiKey: AVSZJJQYCBYHBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.61
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  74.21
• 氢给体数：
  1.0
• 氢受体数：
  5.0

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile 在 吡啶 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 N-[2-[(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-yl)amino]ethyl]-2,4-dinitrobenzamide
  参考文献：
  名称：

  Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: Potential PET imaging agents for tumor detection

  摘要：

  Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[F-18]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([F-18]FEMPPC, [F-18]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[F-18]fluoro-4-nitrobenzamide ([F-18]FCMPPN, [F-18]2), have been designed and successively labeled with F-18 by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [F-18]1 and [F-18]2 with those of [F-18]FDG and L-[F-18]FET in S180 tumor cells. Furthermore, the tumor uptake of [F-18]1 and [F-18]2 was assessed in mice bearing S180 tumor and compared with [F-18]FDG and L-[F-18]FET in the same animal model. In vitro cell uptake studies showed [F-18]1 had higher uptake than [F-18]FDG, [F-18]2 and L-[F-18]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [F-18]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[F-18]FET (2.43, 2.54, 2.93 and 2.95) and [F-18]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [F-18]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[F-18]FET before 30 min and [F-18]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [F-18]1 were superior to those of [F-18]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [F-18]1 at 30 min were higher than those of L-[F-18]FET at the same time point. MicroPET image of [F-18]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [F-18]1 could be a new probe for PET tumor imaging. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.072
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 3-氨基-4-氰基吡唑 在 溶剂黄146 作用下， 以85 %的产率得到5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile
  参考文献：
  名称：

  一些新型吡唑并[1,5-a]嘧啶的制备及其抗氧化、抗菌（MIC和ZOI）活性以及对MCF-7细胞系的细胞毒作用的评价

  摘要：

  本研究旨在合成一些新型吡唑并[1,5-a]嘧啶衍生物，并研究其生物活性。这些化合物表现出良好至高的抗氧化活性[2,2-二苯基-1-三硝基苯肼（DPPH）自由基清除能力]。其中，5-(2-乙氧基-2-氧代乙基)-7-羟基-2-甲基吡唑并[1,5-a]嘧啶-3-甲酸乙酯(3h)表现出最高的抗氧化活性[半最大抑制浓度(与作为标准化合物的抗坏血酸(IC 50 =13.53μM)相比，IC 50 ) = 15.34μM ] 。研究了它们对两种革兰氏阳性菌（枯草芽孢杆菌和金黄色葡萄球菌）和两种革兰氏阴性菌（铜绿假单胞菌和大肠杆菌）的抗菌活性。结果表明，7-羟基-5-苯基吡唑并[1,5-a]嘧啶-3-甲酸乙酯( 3i )对革兰氏阳性枯草芽孢杆菌的抗菌活性最好[抑菌圈(ZOI)=23.0±1.4] mm，最低抑菌浓度 (MIC)=312 μM]。此外，还评估了这些化合物对乳腺癌细胞系 [人乳腺癌 (MCF-7)]

  DOI：

  10.1002/cbdv.202301146

文献信息

• [EN] SUBSTITUTED PYRAZOLO/IMIDAZOLO BICYCLIC COMPOUNDS AS PDE2 INHIBITORS<br/>[FR] COMPOSÉS BICYCLIQUES PYRAZOLO/IMIDAZOLO SUBSTITUÉS EN TANT QU'INHIBITEURS DE PDE2
  申请人：MERCK SHARP & DOHME

  公开号：WO2016209749A1

  公开（公告）日：2016-12-29

  The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

  本发明涉及式I的嘧啶羧酰胺化合物，其可用作治疗与磷酸二酯酶2（PDE2）相关的中枢神经系统疾病的治疗剂。本发明还涉及利用这些化合物治疗神经系统和精神疾病，如精神分裂症、精神病、帕金森病、帕金森病痴呆（PDD）或亨廷顿病，以及与纹状体功能不足或基底节功能障碍相关的疾病。
• 吡唑并[1,5-a]嘧啶氮芥衍生物及其制备方法 和肿瘤治疗应用
  申请人：北京师范大学

  公开号：CN103626776B

  公开（公告）日：2017-02-15

  本发明涉及具有式I结构的吡唑并[1，5‑a]嘧啶氮芥衍生物或其可药用盐，以及其用途。药理实验表明，该类化合物或其可药用盐对多种肿瘤细胞的增殖具有抑制作用。不仅如此，该类化合物还具有毒性较小，对肿瘤细胞具有选择性的优势，是一种具有双功能的抗肿瘤药物。同时，该类化合物易于合成，总产率较高。种种优势，显示此类化合物具有成为肿瘤治疗药物的巨大潜力。
• One-pot three-component synthesis of novel pyrano[3,2-e]pyrazolo[1,5-a]pyrimidines and investigation of their biological activities
  作者：Mohammad Mehdi Vahedi、Sakineh Asghari、Mahmood Tajbakhsh、Mojtaba Mohseni、Asieh Khalilpour

  DOI：10.1016/j.molstruc.2023.135446

  日期：2023.7

  In this study, pyrano[3,2-e]pyrazaolo[1,5-a]pyrimidine derivatives were produced in high yields (80–89%), at room temperature, by three-component reactions involving alkyl isocyanides, dialkyl acetylenedicarboxylates, and 7‑hydroxy pyrazolo[1,5-a]pyrimidines. Using FT-IR, 1H and 13C NMR, and mass spectral data, the structure of the synthesized compounds was identified. The created molecules were tested

  在这项研究中，吡喃并[3,2- e ]吡唑并[1,5- a ]嘧啶衍生物在室温下以高产率（80-89％）通过涉及烷基异氰化物，二烷基乙炔二羧酸酯，和 7-羟基吡唑并[1,5- a ]嘧啶。使用 FT-IR、1 H 和13 C NMR 以及质谱数据，鉴定了合成化合物的结构。所创建的分子针对癌症、细菌和自由基进行了测试，以评估它们的有效性。确定测试物质是否对 MCF-7（乳腺癌）和 MCF-10（乳腺上皮）细胞系具有任何细胞毒性作用。化合物4l与其他化合物相比，显示出最有效的抗癌活性 (IC 50 =19.70±0.89 µM)，与标准药物依托泊苷 (IC 50 = 18.71±1.09 µM)大致相当。此外，还使用 ​​2,2-二苯基-1-苦基肼 (DPPH) 测定法研究了产品的抗氧化特性。结果表明，化合物 4 h 具有最高的自由基清除作用（IC 50 = 12.12±0.40 µM），非常接近抗坏血酸的值（IC
• Substituted pyrazolo/imidazolo bicyclic compounds as PDE2 inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10647727B2

  公开（公告）日：2020-05-12

  The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

  本发明涉及式 I 的嘧啶羧酰胺化合物，该化合物可作为治疗剂用于治疗与磷酸二酯酶 2 (PDE2)相关的中枢神经系统疾病。本发明还涉及使用此类化合物治疗神经和精神疾病，如精神分裂症、精神病、帕金森病、帕金森病痴呆（PDD）或亨廷顿病，以及与纹状体功能低下或基底节功能障碍相关的疾病。
• Preparation and bioevaluation of 99mTc nitrido radiopharmaceuticals with pyrazolo[1,5-a]pyrimidine as tumor imaging agents
  作者：Rui Ding、Yong He、Jingli Xu、Hang Liu、Xiao Wang、Man Feng、Chuanmin Qi、Junbo Zhang、Cheng Peng

  DOI：10.1007/s00044-011-9558-8

  日期：2012.4

  The 7-(2-aminoethylamino)-5-methyl-3-cyanopyrazolo[1,5-a]pyrimidine (AMCPP) was synthesized and conjugated with N-mercaptoacetylglycine (MAG), N-mercaptoacetylphenylalanine (MAF), and N-mercaptoacetylvaline (MAA), respectively. These three compounds were labeled successfully with [(TcN)-Tc-99m](2+) intermediate in high radiochemical purities. Biodistribution in tumor-bearing mice demonstrated that the three new complexes showed high tumor-to-muscle (T/M) ratios and rapid clearance from the blood, muscle, liver, kidney, and lung. Among them, the (TcN)-Tc-99m-MAG-AMCPP showed the most favorable characteristics. The tumor/blood and tumor/muscle ratios reached 1.50 and 1.15 at 30 min post-injection, 2.20 and 1.83 at 60 min post-injection.