4H-[1,2,4]三唑并[1,5-A]嘧啶-7-酮,5-甲基-2-三氟甲基- | 198953-53-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 中文名称: 4H-[1,2,4]三唑并[1,5-A]嘧啶-7-酮,5-甲基-2-三氟甲基-
• 英文名称: 5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5-a]pyrimidin-7-one
• 英文别名: 5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one；5-Methyl-2-trifluoromethyl-4H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one；5-methyl-2-(trifluoromethyl)-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one
• CAS: 198953-53-6
• 化学式: C₇H₅F₃N₄O
• mdl: MFCD01846630
• 分子量: 218.138
• InChiKey: RCFXSBDEUTWHMQ-UHFFFAOYSA-N

物化性质

• 沸点：
  199.4±50.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  57.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4H-[1,2,4]三唑并[1,5-A]嘧啶-7-酮,5-甲基-2-三氟甲基- 在 三氯氧磷 作用下， 反应 4.0h， 以90%的产率得到7-氯-5-甲基-2-(三氟甲基)-[1,2,4]噻唑并[1,5-a]嘧啶
  参考文献：
  名称：

  New Trifluoromethyl Triazolopyrimidines as Anti-Plasmodium falciparum Agents

  摘要：

  根据世界卫生组织的数据，全球一半的人口（约 33 亿人）有可能罹患疟疾。每年有近 70 万人死于疟疾。人类对疟疾的控制仍然依赖化疗。抗药性是一个限制因素，因此寻找新药非常重要。我们设计并合成了新的 2-(三氟甲基)[1,2,4]三唑并[1,5-a]嘧啶衍生物，其基础是生物异构取代抗疟疾化合物甲氟喹和阿莫地喹上的官能团。这种方法使我们能够研究以下因素的影响：(i)环的生物异构取代；(ii)[1,2,4]三唑并[1,5-a]嘧啶支架 2 位的 CF3 基团取代；以及(iii)杂环 7 位的一系列胺取代基；对恶性疟原虫体外活性的影响。根据对接模拟，合成的化合物能够通过强氢键与恶性疟原虫二氢烟酸脱氢酶（PfDHODH）相互作用。在[1,2,4]三唑并[1,5-a]嘧啶环的 2 位上存在三氟甲基可提高药物活性。在抗 HRP2 和次黄嘌呤试验中，发现 13 种化合物具有活性，IC50 值从 0.023 到 20 µM。最有活性的衍生物 5、8、11 和 16 的选择性指数（SI）从 1,003 到 18,478 不等。

  DOI：

  10.3390/molecules17078285
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 5-(三氟甲基)-4H-1,2,4-噻唑-3-胺 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以84%的产率得到4H-[1,2,4]三唑并[1,5-A]嘧啶-7-酮,5-甲基-2-三氟甲基-
  参考文献：
  名称：

  三唑并嘧啶，吡唑并嘧啶和喹啉衍生物的抗恶性疟原虫活性比较及鉴定新的Pf DHODH抑制剂

  摘要：

  在这项工作中，我们设计并合成了35种新的三唑并嘧啶，吡唑并嘧啶和喹啉衍生物作为恶性疟原虫抑制剂（3D7株）。三十种化合物表现出抗恶性疟原虫活性，IC 50值范围为0.030至9.1μM。[1,2,4]三唑并[1,5- a ]嘧啶衍生物比吡唑并[1,5- a ]嘧啶和喹啉类似物更有效。化合物20，21，23和24是最有效的抑制剂，具有IC 50值在0.030-0.086μM范围内，与氯喹等效。此外，这些化合物具有选择性，对人肝癌细胞系HepG2没有细胞毒活性。所有的[1,2,4]三唑并[1,5- a ]嘧啶衍生物均在低微摩尔至低纳摩尔范围（IC 50值为0.08-1.3μM）内抑制Pf DHODH活性，并且未显示出对Hs DHODH的明显抑制作用同源物（50μM时为0-30％）。分子对接研究表明[1,2,4]三唑并[1,5- a ]嘧啶衍生物与Pf DHODH的结合方式，与Pf DHODH酶

  DOI：

  10.1016/j.ejmech.2020.112941

文献信息

• Comparative study between the anti-P. falciparum activity of triazolopyrimidine, pyrazolopyrimidine and quinoline derivatives and the identification of new PfDHODH inhibitors
  作者：Flávia F. Silveira、Juliana O. de Souza、Lucas V.B. Hoelz、Vinícius R. Campos、Valquíria A.P. Jabor、Anna C.C. Aguiar、M. Cristina Nonato、Magaly G. Albuquerque、Rafael V.C. Guido、Nubia Boechat、Luiz C.S. Pinheiro

  DOI：10.1016/j.ejmech.2020.112941

  日期：2021.1

  pyrazolopyrimidine and quinoline derivatives as P. falciparum inhibitors (3D7 strain). Thirty compounds exhibited anti-P. falciparum activity, with IC50 values ranging from 0.030 to 9.1 μM. The [1,2,4]triazolo[1,5-a]pyrimidine derivatives were more potent than the pyrazolo[1,5-a]pyrimidine and quinoline analogues. Compounds 20, 21, 23 and 24 were the most potent inhibitors, with IC50 values in the range of 0.030

  在这项工作中，我们设计并合成了35种新的三唑并嘧啶，吡唑并嘧啶和喹啉衍生物作为恶性疟原虫抑制剂（3D7株）。三十种化合物表现出抗恶性疟原虫活性，IC 50值范围为0.030至9.1μM。[1,2,4]三唑并[1,5- a ]嘧啶衍生物比吡唑并[1,5- a ]嘧啶和喹啉类似物更有效。化合物20，21，23和24是最有效的抑制剂，具有IC 50值在0.030-0.086μM范围内，与氯喹等效。此外，这些化合物具有选择性，对人肝癌细胞系HepG2没有细胞毒活性。所有的[1,2,4]三唑并[1,5- a ]嘧啶衍生物均在低微摩尔至低纳摩尔范围（IC 50值为0.08-1.3μM）内抑制Pf DHODH活性，并且未显示出对Hs DHODH的明显抑制作用同源物（50μM时为0-30％）。分子对接研究表明[1,2,4]三唑并[1,5- a ]嘧啶衍生物与Pf DHODH的结合方式，与Pf DHODH酶
• New Trifluoromethyl Triazolopyrimidines as Anti-Plasmodium falciparum Agents
  作者：Núbia Boechat、Luiz C. S. Pinheiro、Thiago S. Silva、Anna C. C. Aguiar、Alcione S. Carvalho、Monica M. Bastos、Carolina C. P. Costa、Sergio Pinheiro、Angelo C. Pinto、Jorge S. Mendonça、Karen D. B. Dutra、Alessandra L. Valverde、Osvaldo A. Santos-Filho、Isabela P. Ceravolo、Antoniana U. Krettli

  DOI：10.3390/molecules17078285

  日期：——

  According to the World Health Organization, half of the World’s population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF3 group substituted at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. According to docking simulations, the synthesized compounds are able to interact with P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC50 values ranging from 0.023 to 20 µM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.

  根据世界卫生组织的数据，全球一半的人口（约 33 亿人）有可能罹患疟疾。每年有近 70 万人死于疟疾。人类对疟疾的控制仍然依赖化疗。抗药性是一个限制因素，因此寻找新药非常重要。我们设计并合成了新的 2-(三氟甲基)[1,2,4]三唑并[1,5-a]嘧啶衍生物，其基础是生物异构取代抗疟疾化合物甲氟喹和阿莫地喹上的官能团。这种方法使我们能够研究以下因素的影响：(i)环的生物异构取代；(ii)[1,2,4]三唑并[1,5-a]嘧啶支架 2 位的 CF3 基团取代；以及(iii)杂环 7 位的一系列胺取代基；对恶性疟原虫体外活性的影响。根据对接模拟，合成的化合物能够通过强氢键与恶性疟原虫二氢烟酸脱氢酶（PfDHODH）相互作用。在[1,2,4]三唑并[1,5-a]嘧啶环的 2 位上存在三氟甲基可提高药物活性。在抗 HRP2 和次黄嘌呤试验中，发现 13 种化合物具有活性，IC50 值从 0.023 到 20 µM。最有活性的衍生物 5、8、11 和 16 的选择性指数（SI）从 1,003 到 18,478 不等。
• Novel Selective Inhibitor of <i>Leishmania (Leishmania) amazonensis</i> Arginase
  作者：Edson R. da Silva、Nubia Boechat、Luiz C. S. Pinheiro、Monica M. Bastos、Carolina C. P. Costa、Juliana C. Bartholomeu、Talita H. da Costa

  DOI：10.1111/cbdd.12566

  日期：2015.11

  Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and trypanothione biosynthesis. The central role of arginase in Leishmania (Leishmania) amazonensis was demonstrated by the generation of two mutants: one with an arginase lacking the glycosomal addressing signal and one in which the arginase‐coding gene was knocked out. Both of these mutants exhibited decreased infectivity. Thus, arginase seems to be a potential drug target for Leishmania treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the [1,2,4]triazolo[1,5‐a]pyrimidine system were tested against Leishmania (Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5‐a]pyrimidine scaffold containing R1 = CF3 exhibited greater activity against the arginase rather than when the substituent R1 = CH3 in the 2‐position. The novel compound 2‐(5‐methyl‐2‐(trifluoromethyl)‐[1,2,4]triazolo[1,5‐a]pyrimidin‐7‐yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non‐competitive mechanism, with the Ki and IC50 values for arginase inhibition estimated to be 17 ± 1 μm and 16.5 ± 0.5 μm, respectively. These results can guide the development of new drugs against leishmaniasis based on [1,2,4]triazolo[1,5‐a]pyrimidine derivatives targeting the arginase enzyme.
• Hydrogen-bonded chains in 5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5-<i>a</i>]pyrimidin-7(4<i>H</i>)-one and hydrogen-bonded chains of rings in 5-amino-3-trifluoromethyl-1<i>H</i>-1,2,4-triazole–5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5-<i>a</i>]pyrimidin-7(4<i>H</i>)-one (1/1), the co-crystal of a reaction product and one of its precursors
  作者：Nubia Boechat、Karen D. B. Dutra、Alessandra L. Valverde、Solange M. S. V. Wardell、John N. Low、Christopher Glidewell

  DOI：10.1107/s0108270104020256

  日期：2004.10.15

  In the title compounds, C7H5F3N4O, (I), and C3H3F3N4.-C7H5F3N4O, (II), all of the molecular components exhibit some polarization of their molecular - electronic structures. The molecules in ( I) are linked into simple C( 6) chains, while in ( II), the components are linked by a combination of two-centre N - H...N and N - H...O, and three-centre N-H ...(O, N) hydrogen bonds into chains containing R-1(2)(5), R-2(1)(6) and R-2(2)(8) rings.
• Zohdi, Hussein F., Journal of Chemical Research, Miniprint, 1997, # 11, p. 2378 - 2394
  作者：Zohdi, Hussein F.

  DOI：——

  日期：——