5-(trifluoromethyl)-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one | 40775-91-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-(trifluoromethyl)-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one
• 英文别名: 5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
• CAS: 40775-91-5
• 化学式: C₆H₃F₃N₄O
• 分子量: 204.111
• InChiKey: KCCYYMMHNVDRKT-UHFFFAOYSA-N

物化性质

• 熔点：
  263 °C
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.85
• 重原子数：
  14.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-(trifluoromethyl)-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one 在 三氯氧磷 作用下， 反应 1.0h， 生成 7-chloro-5-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  基于喹啉甲酰胺核心部分的化合物抑制恶性疟原虫 falcipain-2：设计、合成和抗疟功效研究

  摘要：

  以 Falcipain-2 (FP2) 为靶点开发抗疟药是抗疟药发现和开发中一个很有前景的既定概念。FP2 是疟原虫恶性疟原虫的木瓜蛋白酶家族半胱氨酸蛋白酶的成员，在血红蛋白降解途径中具有重要作用。设计、合成了一系列新的喹啉甲酰胺类化合物并评估了其抗疟活性。我们将分子杂交策略与计算机药物设计相结合，以开发 FP2 抑制剂。发现Qs17、Qs18、Qs20和Qs21抑制 FP2 的体外结果在低微摩尔范围内，IC 50分别为 4.78、7.37、2.14 和 2.64 µM。在 25 种合成化合物中，四种化合物显示出显着的抗疟活性。这些化合物还比已建立的 FP2 抑制剂 E-64 更好地描述了形态学和食物液泡异常。总的来说，这些芳香族取代的喹啉甲酰胺可以作为开发新型抗疟药的有希望的先导。

  DOI：

  10.1016/j.bioorg.2020.104514
• 作为产物：
  描述：

  三氟乙酰乙酸乙酯 、 3-氨基-1,2,4-三氮唑 在 溶剂黄146 作用下， 反应 6.0h， 生成 5-(trifluoromethyl)-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one
  参考文献：
  名称：

  [EN] SUBSTITUTED TRIAZOLO BICYCLICCOMPOUNDS AS PDE2 INHIBITORS
  [FR] BICYCLO-COMPOSÉS DE TRIAZOLE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE PDE2

  摘要：

  本发明涉及一种用于治疗与磷酸二酯酶2（PDE2）相关的中枢神经系统疾病的式（I）的取代三唑杂双环化合物，该化合物可用作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神经节功能障碍相关的化合物的用途。

  公开号：

  WO2017000277A1

文献信息

• [EN] [1,2,4]-TRIAZOLO [1,5-A]-PYRIMIDINYL DERIVATIVES SUBSTITUTED WITH PIPERIDINE, MORPHOLINE OR PIPERAZINE AS OGA INHIBITORS<br/>[FR] DÉRIVÉS DE [1,2,4]-TRIAZOLO [1,5-A]-PYRIMIDINYLE SUBSTITUÉS PAR DE LA PIPÉRIDINE, DE LA MORPHOLINE OU DE LA PIPÉRAZINE UTILISÉS EN TANT QU'INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018154133A1

  公开（公告）日：2018-08-30

  The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations.

  本发明涉及O-GlcNAc水解酶（OGA）抑制剂。该发明还涉及包括这些化合物的药物组合物，用于制备这些化合物和组合物的方法，以及利用这些化合物和组合物预防和治疗抑制OGA有益的疾病的用途，如tau病变病，特别是阿尔茨海默病或进行性上颌核瘤；以及伴有tau病理的神经退行性疾病，特别是由C90RF72突变引起的肌萎缩侧索硬化或颞叶前叶痴呆症。
• Substituted triazolo bicyclic compounds as PDE2 inhibitors
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US10357481B2

  公开（公告）日：2019-07-23

  The present invention is directed to substituted triazolo bicyclic 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 的取代三唑并双环化合物，其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。
• Lead Optimization of Aryl and Aralkyl Amine-Based Triazolopyrimidine Inhibitors of <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase with Antimalarial Activity in Mice
  作者：Ramesh Gujjar、Farah El Mazouni、Karen L. White、John White、Sharon Creason、David M. Shackleford、Xiaoyi Deng、William N. Charman、Ian Bathurst、Jeremy Burrows、David M. Floyd、David Matthews、Frederick S. Buckner、Susan A. Charman、Margaret A. Phillips、Pradipsinh K. Rathod

  DOI：10.1021/jm200265b

  日期：2011.6.9

  Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom. Herein, we describe systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the series. These studies led to the identification of two new substituted aniline moieties (4-SF(5)-Ph and 3,5-Di-F-4-CF(3)-Ph), which, when coupled to the triazolopyrimidine ring, showed good plasma exposure and better efficacy in the Plasmodium berghei mouse model of the disease than previously reported compounds from the series.
• Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitors with Potent and Selective Activity against the Malaria Parasite <i>Plasmodium falciparum</i>
  作者：Margaret A. Phillips、Ramesh Gujjar、Nicholas A. Malmquist、John White、Farah El Mazouni、Jeffrey Baldwin、Pradipsinh K. Rathod

  DOI：10.1021/jm8001026

  日期：2008.6.1

  A Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitor that is potent (K(I) = 15 nM) and species-selective (>5000-fold over the human enzyme) was identified by high-throughput screening. The substituted triazolopyrimidine and its structural analogues were produced by an inexpensive three-step synthesis, and the series showed good association between PfDHODH inhibition and parasite toxicity. This study has identified the first nanomolar PfDHODH inhibitor with potent antimalarial activity in whole cells (EC(50) = 79 nM).
• Hlavka, Joseph J.; Bitha, Panayota; Lin, Yang-i, Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1317 - 1322
  作者：Hlavka, Joseph J.、Bitha, Panayota、Lin, Yang-i、Strohmeyer, Timothy

  DOI：——

  日期：——