ethyl 5-cyano-6-(piperazin-1-yl)-2-(trifluoromethyl)nicotinate | 266680-09-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 5-cyano-6-(piperazin-1-yl)-2-(trifluoromethyl)nicotinate
• 英文别名: ethyl 5-cyano-6-piperazin-1-yl-2-(trifluoromethyl)nicotinate；ethyl 5-cyano-6-piperazin-1-yl-2-(trifluoromethyl)pyridine-3-carboxylate
• CAS: 266680-09-5
• 化学式: C₁₄H₁₅F₃N₄O₂
• 分子量: 328.294
• InChiKey: BJNAOUVCLVYZQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  482.4±45.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  >49.2 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 5-cyano-6-(piperazin-1-yl)-2-(trifluoromethyl)nicotinate 在 4-二甲氨基吡啶 、 乙醇 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.5h， 生成 5-cyano-6-(4-(2-phenylacetyl)piperazine-1-yl)-2-(trifluoromethyl)nicotinic acid-2-hydroxyethyl ester
  参考文献：
  名称：

  一种靶向神经炎症嘌呤能P2Y12受体的PET成像剂的制备方法及应用

  摘要：

  本发明属于生物医药领域，涉及一种新型的靶向神经炎症嘌呤能P2Y12受体的氟18标记的PET成像剂，该成像剂可用于观察神经炎症疾病变化。本发明还公开了该成像剂的制备方法，包括两条合成路线，得到化合物[18F]13a，以及公开了利用该成像剂对正常小鼠，荷瘤小鼠，癫痫小鼠及衰老小鼠进行PET/CT成像的方法，其具有高亲和力、高选择性、高脑摄取率及低血浆代谢水平等优点，是一种具有潜在临床应用价值的PET探针。

  公开号：

  CN118344351A
• 作为产物：
  描述：

  乙氧基-2-亚甲基三氟乙酰乙酸乙酯 在 草酰氯 、 sodium ethanolate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 32.33h， 生成 ethyl 5-cyano-6-(piperazin-1-yl)-2-(trifluoromethyl)nicotinate
  参考文献：
  名称：

  A novel series of piperazinyl-pyridine ureas as antagonists of the purinergic P2Y12 receptor

  摘要：

  A novel series of P2Y(12) antagonists for development of drugs within the antiplatelet area is presented. The synthesis of the piperazinyl-pyridine urea derivatives and their structure-activity relationships (SAR) are described. Several compounds showed P2Y(12) antagonistic activities in the sub-micromolar range. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.088

文献信息

• New Pyridine Analogues II
  申请人：Brickmann Kay

  公开号：US20070244088A1

  公开（公告）日：2007-10-18

  The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y 12 inhibitors and as anti-thrombotic agents, etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新的Formula (I)的吡啶类似物，涉及制备这类化合物的方法，它们在医学上的用途，特别是作为P2Y12受体拮抗剂和抗血栓药物等，它们在心血管疾病中作为药物的用途，以及含有它们的药物组合物。
• Novel Pyridine Compounds
  申请人：Bach Peter

  公开号：US20090227555A2

  公开（公告）日：2009-09-10

  The present invention relates to certain novel pyridin compounds of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-thrombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新型的Formula (I)吡啶化合物，以及制备这些化合物的方法，它们作为P2Y12抑制剂和抗血栓剂等的用途，以及它们的制备过程，它们在心血管疾病中作为药物的用途，以及包含它们的制药组合物。
• Pyridine Analogues II
  申请人：Brickmann Kay

  公开号：US20090186876A1

  公开（公告）日：2009-07-23

  The present invention relates to certain new pyridin analogues of Formula (I) [Chemical formula should be inserted here. Please see paper copy] Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y 12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新的Formula (I) [化学式应在此处插入。请参阅纸质副本]的吡啶类似物，以及制备这些化合物的过程，它们在医学上的用途，特别是作为P2Y12抑制剂和抗血栓药物等，它们在心血管疾病中用作药物以及包含它们的制药组合物。
• WO2006/73361
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis, structure–property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor
  作者：Peter Bach、Jonas Boström、Kay Brickmann、J.J.J. van Giezen、Robert D. Groneberg、Darren M. Harvey、Michael O'Sullivan、Fredrik Zetterberg

  DOI：10.1016/j.ejmech.2013.04.007

  日期：2013.7

  The present paper describes the development of a new series of P2Y(12) receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 mu M, aq solubility <0.1 mu M, microsomal CLint (HLM) >= 300 mu M/min/mg). By replacement of the urea functionality with a sulfonylurea group we observed increased affinity along with improved stability and solubility as exemplified by 47 (IC50 binding affinity = 0.042 mu M, aq solubility = 90 mu M, microsomal CLint (HLM) = 70 mu M/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 mu M, aq solubility = 83 mu M, microsomal CLint (HLM) = 28 mu M/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality. (C) 2013 Elsevier Masson SAS. All rights reserved.