ethyl 6-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-5-cyano-2-methylnicotinate | 898227-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 6-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-5-cyano-2-methylnicotinate
• 英文别名: Ethyl 6-{3-[(tert-butoxycarbonyl)amino]azetidin-1-yl}-5-cyano-2-methylnicotinate；ethyl 5-cyano-2-methyl-6-[3-[(2-methylpropan-2-yl)oxycarbonylamino]azetidin-1-yl]pyridine-3-carboxylate
• CAS: 898227-69-5
• 化学式: C₁₈H₂₄N₄O₄
• 分子量: 360.413
• InChiKey: NMRKJMWWTCJMAC-UHFFFAOYSA-N

物化性质

• 沸点：
  549.1±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 6-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-5-cyano-2-methylnicotinate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 17.0h， 生成 ethyl 6-(3-(3-((5-chlorothiophen-2-yl)sulfonyl)ureido)azetidin-1-yl)-5-cyano-2-methylnicotinate
  参考文献：
  名称：

  Synthesis, structure–property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.04.007
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 sodium hydride 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 19.0h， 生成 ethyl 6-(3-((tert-butoxycarbonyl)amino)azetidin-1-yl)-5-cyano-2-methylnicotinate
  参考文献：
  名称：

  WO2006/73361

  摘要：

  公开号：

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。
• Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state
  作者：Alessandro Villa、Barbara Klein、Bieneke Janssen、Jordi Pedragosa、Giovanna Pepe、Bastian Zinnhardt、Danielle J. Vugts、Paolo Gelosa、Luigi Sironi、Wissam Beaino、Annelaure Damont、Frédéric Dollé、Benoit Jego、Alexandra Winkeler、Dieter Ory、Olof Solin、Johnny Vercouillie、Uta Funke、Sandra Laner-Plamberger、Linda V. Blomster、Palle Christophersen、Elisabetta Vegeto、Ludwig Aigner、Andreas Jacobs、Anna M. Planas、Adriana Maggi、Albert D. Windhorst

  DOI：10.7150/thno.25572

  日期：——

  Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess the efficacy of therapies aimed to reduce the tissue damaging activities of microglia and/or to promote the protective potential of these cells, suitable pre-clinical and clinical tools for the in vivo analysis of microglia activities and dynamics are required. The aim of this work was to identify new translational markers of the anti-inflammatory / protective state of microglia for the development of novel PET tracers.

  小胶质细胞是影响中枢神经系统的神经疾病和神经退行性疾病治疗干预的潜在靶点。为了评估旨在减少小胶质细胞损伤组织活动和/或促进这些细胞保护潜力的疗法的有效性，需要合适的临床前和临床工具来进行小胶质细胞活动和动态的体内分析。本研究的目标是识别小胶质细胞抗炎/保护状态的新转化标记物，以便开发新的PET示踪剂。
• 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
  申请人：Andersen Soren

  公开号：US20080312208A1

  公开（公告）日：2008-12-18

  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 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)式吡啶类似物，化学式应在此处插入。请参见纸质副本Formula (I)，以及制备这些化合物的过程，它们作为P2Y12抑制剂和抗血栓剂等的效用，它们在心血管疾病中作为药物的用途以及含有它们的制药组合物。
• 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。