(±)-ethyl 6-[3-(3-tert-butoxy-3-oxopropyl)piperazin-1-yl]-5-cyano-2-(trifluoromethyl)nicotinate | 898227-31-1

• 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 6-[3-(3-tert-butoxy-3-oxopropyl)piperazin-1-yl]-5-cyano-2-(trifluoromethyl)nicotinate
• 英文别名: Ethyl 6-[3-(3-tert-butoxy-3-oxopropyl)piperazin-1-yl]-5-cyano-2-(trifluoromethyl)nicotinate；ethyl 5-cyano-6-[3-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]piperazin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylate
• CAS: 898227-31-1
• 化学式: C₂₁H₂₇F₃N₄O₄
• 分子量: 456.465
• InChiKey: VHQALQHLEOAPHH-UHFFFAOYSA-N

物化性质

• 沸点：
  561.8±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (±)-ethyl 6-[3-(3-tert-butoxy-3-oxopropyl)piperazin-1-yl]-5-cyano-2-(trifluoromethyl)nicotinate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 28.5h， 生成 (±)-3-{1-({[(5-chloro-2-thienyl)sulfonyl]amino}carbonyl)-4-[3-cyano-5-[ethoxy(hydroxy)methyl]-6-(trifluoromethyl)pyridin-2-yl]piperazin-2-yl}propanoic acid
  参考文献：
  名称：

  WO2006/73361

  摘要：

  公开号：
• 作为产物：
  描述：

  6-氯-5-氰基-2-(三氟甲基)烟酸乙酯 、 (±)-tert-butyl 3-(piperazin-2-yl)propanoate 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以40%的产率得到(±)-ethyl 6-[3-(3-tert-butoxy-3-oxopropyl)piperazin-1-yl]-5-cyano-2-(trifluoromethyl)nicotinate
  参考文献：
  名称：

  New Pyridine Analogues II

  摘要：

  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。

  公开号：

  US20070244088A1

文献信息

• 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。
• 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.
• NOVEL PYRIDINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1836189A1

  公开（公告）日：2007-09-26
• NEW PYRIDINE ANALOGUES
  申请人：AstraZeneca AB

  公开号：EP2041111A1

  公开（公告）日：2009-04-01