7-氯-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈 | 138904-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 7-氯-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈
• 英文名称: 7-chloro-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
• 英文别名: 7-chloro-5-methylpyrazolo<1,5-a>pyrimidine-3-carbonitrile
• CAS: 138904-34-4
• 化学式: C₈H₅ClN₄
• 分子量: 192.607
• InChiKey: FZHJDKNVOBPMFQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  7-氯-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 16.5h， 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：

  5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile 在 吡啶 、 三氯氧磷 作用下， 反应 2.0h， 生成 7-氯-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRAZOLO/IMIDAZOLO BICYCLIC COMPOUNDS AS PDE2 INHIBITORS
  [FR] COMPOSÉS BICYCLIQUES PYRAZOLO/IMIDAZOLO SUBSTITUÉS EN TANT QU'INHIBITEURS DE PDE2

  摘要：

  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。

  公开号：

  WO2016209749A1

文献信息

• An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity
  作者：SOMESHWAR DESHMUKH、KUNAL DINGORE、VISHWAS GAIKWAD、MADHUKAR JACHAK

  DOI：10.1007/s12039-016-1141-x

  日期：2016.9

  afforded pyrazolo-pyrido-pyrimidine 5 and dihydrofuro-pyrido-pyrazolo-pyrimidine 6. All synthesized compounds were screened for antimicrobial activity. 7-Hydrazinyl-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile 2 was utilized as a precursor to afford pyrazolo[3,4-d]pyrimidines 13a-b. However, dioxopyrrolidindolinylamio-pyrazolo-pyrimidines 14a-b, and dioxoisoindolin-pyrazolo-pyrimidines 14c-d were also

  通过使用7-肼基-5-甲基吡唑并[1,5 - a ]嘧啶-3-甲腈1和7-氨基-5-甲基吡唑并[1，1 ]合成了一系列新的吡唑并[1,5- a ]嘧啶衍生物。 5 - a ]嘧啶-3-腈2作为前体。吡唑并[3,4- d ]嘧啶3a–b是通过从1开始的三步反应合成的。化合物1用于合成二氧杂吡咯并吲哚基吡唑并嘧啶4a-b和二氧异吲哚并吡唑并嘧啶4c-d。另外，化合物4a-d使用深共熔溶剂（DES）合成。这种使用DES的方法具有许多优点，例如良性环境，高产量，可扩展和简单的后处理程序。类似地，将2与α-乙酰基-γ-丁内酯的环缩合得到吡唑并-吡啶并-嘧啶5和二氢呋喃-吡啶并-吡唑并-嘧啶6。筛选所有合成的化合物的抗微生物活性。 利用7-肼基-5-甲基吡唑并[1，5-a]嘧啶-3-腈2作为前体，得到吡唑并[3，4-d]嘧啶13a-b。然而，也使用深共晶溶剂获得二氧杂吡咯烷基吲哚基吡喃并吡唑并嘧啶14
• [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。
• 18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography
  作者：Jingli Xu、Hang Liu、Guixia Li、Yong He、Rui Ding、Xiao Wang、Man Feng、Shuting Zhang、Yurong Chen、Shilei Li、Mingxia Zhao、Yingruo Li、Chuanmin Qi、Yonghong Dang

  DOI：10.3390/molecules17043774

  日期：——

  hylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl acetate ([18F]3), 7-(2-[18F]fluoroethylamino)-5-(hydroxymethyl)pyrazolo[1,5-a]- pyrimidine-3-carbonitrile ([18F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)-2-(2-[18F]fluoro-4-nitrobenzamido)hexanoic acid ([18F]5). The radiolabeled probes were synthesized by nucleophilic substitution of the corresponding tosylate and nitro precursors

  我们之前报道了 18F 标记的吡唑并[1,5-a]嘧啶衍生物：7-(2-[18F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([18F]1) 和N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro-4-nitro-benzamide ([18F]2)。两种化合物的初步生物分布实验表明，它们从排泄组织中的清除率缓慢，这需要进一步研究用 PET 进行肿瘤成像。在这里，我们通过引入酯、羟基和羧基等极性基团修饰了 [18F]1 和 [18F]2，并开发了三种额外的 18F-18 标记的吡唑并[1,5-a]嘧啶衍生物：(3-Cyano-7-( 2-[18F]氟乙氨基)吡唑并[1,5-a]-嘧啶-5-基)乙酸甲
• 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。