1-(3-cyano-5-(ethoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid | 919354-24-8

• 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: 1-(3-cyano-5-(ethoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid
• 英文别名: 1-(3-cyano-5-ethoxycarbonyl-6-methylpyridin-2-yl)piperidine-4-carboxylic acid
• CAS: 919354-24-8
• 化学式: C₁₆H₁₉N₃O₄
• 分子量: 317.345
• InChiKey: JPDCHUPRIIGKND-UHFFFAOYSA-N

物化性质

• 沸点：
  556.5±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3-cyano-5-(ethoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid 、 苯甲磺酰胺 在 N,N'-羰基二咪唑 作用下， 以 丁酮 为溶剂， 反应 7.5h， 以83%的产率得到6-[4-[[(苄基磺酰基)氨基]羰基]哌啶-1-基]-5-氰基-2-甲基烟酸乙酯
  参考文献：
  名称：

  Development of a Multi-Kilogram-Scale Synthesis of AZD1283: A Selective and Reversible Antagonist of the P2Y₁₂ Receptor

  摘要：

  Ethyl 6-chloro-5-cyano-2-methylnicotinate (4) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine acid 10. An amide coupling between 10 and benzylsulfonamide (6) afforded AZD1283 (1) in 79% yield using CDI as coupling reagent. The synthesis has been developed and scaled up to 20 kg batches of 1, supporting preclinical and clinical studies. Development work towards 2-chloropyridine 4 and benzylsulfonamide (6) is included.

  DOI：

  10.1021/op400288v
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 氯化亚砜 、 sodium ethanolate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 18.17h， 生成 1-(3-cyano-5-(ethoxycarbonyl)-6-methylpyridin-2-yl)piperidine-4-carboxylic acid
  参考文献：
  名称：

  Development of a Multi-Kilogram-Scale Synthesis of AZD1283: A Selective and Reversible Antagonist of the P2Y₁₂ Receptor

  摘要：

  Ethyl 6-chloro-5-cyano-2-methylnicotinate (4) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine acid 10. An amide coupling between 10 and benzylsulfonamide (6) afforded AZD1283 (1) in 79% yield using CDI as coupling reagent. The synthesis has been developed and scaled up to 20 kg batches of 1, supporting preclinical and clinical studies. Development work towards 2-chloropyridine 4 and benzylsulfonamide (6) is included.

  DOI：

  10.1021/op400288v

文献信息

• New Pyridine Analogues VII 543
  申请人：Antonsson Thomas

  公开号：US20080176827A1

  公开（公告）日：2008-07-24

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

  本发明涉及某些新型的吡啶类似物，其化学式为(I)，涉及制备这些化合物的工艺，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使用，以及包含它们的药物组合物。
• 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
  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。
• WO2007/8140
  申请人：——

  公开号：——

  公开（公告）日：——
• Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y₁₂ Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283
  作者：Peter Bach、Thomas Antonsson、Ruth Bylund、Jan-Arne Björkman、Krister Österlund、Fabrizio Giordanetto、J. J. J. van Giezen、Søren M. Andersen、Helen Zachrisson、Fredrik Zetterberg

  DOI：10.1021/jm400820m

  日期：2013.9.12

  Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y(12) receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines. In a modified Folts model in dog, both piperidine 3 and azetidine 13 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 mu g/kg/min, respectively. The doses that induced a larger than 3-fold increase in bleeding time were 33 and 100 mu g/kg/min for 3 and 13, respectively. Thus, the therapeutic index (TI) was >= 10 for both compounds. On the basis of these data, compound 3 was progressed into human clinical trials as candidate drug AZD1283.