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 | 919351-41-0

• 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
• 中文名称: 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
• 英文名称: AZD1283
• 英文别名: Ethyl 6-{4-[(Benzylsulfonyl)carbamoyl]piperidin-1-Yl}-5-Cyano-2-Methylpyridine-3-Carboxylate；ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate
• CAS: 919351-41-0
• 化学式: C₂₃H₂₆N₄O₅S
• 分子量: 470.549
• InChiKey: NEMHKCNXXRQYRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 储存条件：
  -20℃

制备方法与用途

AZD1283是一种P2Y12受体拮抗剂，其EC50值为3.0 μg/kg/min，结合的IC50值为11 nM。

反应信息

• 作为反应物：
  描述：

  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 在 sodium hydroxide 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 1.75h， 以91%的产率得到6-(4-{[(benzylsulfonyl)amino]carbonyl}piperidin-1-yl)-5-cyano-2-methylnicotinic acid
  参考文献：
  名称：

  [EN] 2-AMINO-6-ALKYL SUBSTITUTED PYRIDINE DERIVATIVES USEFUL AS P2Y12 INHIBITORS 308
  [FR] DÉRIVÉS DE PYRIDINE SUBSTITUÉS PAR 2-AMINO-6-ALKYLE UTILES COMME INHIBITEURS DE P2Y12

  摘要：

  本发明涉及某些新的Formula（I）的吡啶类似物，以及制备这类化合物的方法，它们作为P2Y12抑制剂和抗血栓药物等的用途，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：

  WO2010005385A1
• 作为产物：
  描述：

  5-氰基-1,6-二氢-2-甲基-6-氧代-3-吡啶羧酸乙酯 在 氯化亚砜 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 、 丁酮 为溶剂， 反应 9.5h， 生成 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

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。
• An Integrated Approach toward NanoBRET Tracers for Analysis of GPCR Ligand Engagement
  作者：Michael P. Killoran、Sergiy Levin、Michelle E. Boursier、Kristopher Zimmerman、Robin Hurst、Mary P. Hall、Thomas Machleidt、Thomas A. Kirkland、Rachel Friedman Ohana

  DOI：10.3390/molecules26102857

  日期：——

  Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) monitoring competitive binding between fluorescent tracers and unmodified test compounds has emerged as a robust and sensitive method to quantify ligand engagement with specific GPCRs genetically fused to NanoLuc luciferase or the luminogenic HiBiT peptide. However, development of fluorescent tracers is often challenging and remains the principal bottleneck for this approach. One way to alleviate the burden of developing a specific tracer for each receptor is using promiscuous tracers, which is made possible by the intrinsic specificity of BRET. Here, we devised an integrated tracer discovery workflow that couples machine learning-guided in silico screening for scaffolds displaying promiscuous binding to GPCRs with a blend of synthetic strategies to rapidly generate multiple tracer candidates. Subsequently, these candidates were evaluated for binding in a NanoBRET ligand-engagement screen across a library of HiBiT-tagged GPCRs. Employing this workflow, we generated several promiscuous fluorescent tracers that can effectively engage multiple GPCRs, demonstrating the efficiency of this approach. We believe that this workflow has the potential to accelerate discovery of NanoBRET fluorescent tracers for GPCRs and other target classes.

  获取有关配体在生物相关条件下与G蛋白偶联受体（GPCRs）相互作用的药理学见解对于药物发现和基础研究至关重要。基于NanoLuc的生物发光共振能量转移（NanoBRET）监测荧光示踪剂与未修改的测试化合物之间的竞争结合已经成为一种强大而敏感的方法，用于量化与特定GPCRs遗传融合到NanoLuc荧光酶或发光HiBiT肽的配体相互作用。然而，开发荧光示踪剂通常具有挑战性，并且仍然是该方法的主要瓶颈。减轻为每个受体开发特定示踪剂的负担的一种方法是使用多功能示踪剂，这是由BRET的固有特异性所实现的。在这里，我们设计了一种集成示踪剂发现工作流程，将机器学习引导的体外筛选具有对GPCRs显示多功能结合的支架与合成策略的混合相结合，以快速生成多个示踪剂候选物。随后，这些候选物在HiBiT标记的GPCRs库中进行了NanoBRET配体结合筛选的结合评估。利用这种工作流程，我们生成了几种可以有效与多个GPCRs相互作用的多功能荧光示踪剂，展示了这种方法的效率。我们相信这种工作流程有潜力加速发现用于GPCRs和其他靶标类别的NanoBRET荧光示踪剂。
• New Pyridine Analogues VIII 518
  申请人：Antonsson Thomas

  公开号：US20080200448A1

  公开（公告）日：2008-08-21

  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.

  本发明涉及某些新的Formula(I)吡啶类似物、制备这些化合物的方法、它们作为P2Y12抑制剂和抗血栓药物等的用途、它们作为心血管疾病药物的使用，以及包含它们的制药组合物。
• Novel Crystalline Forms 2
  申请人：Andersen Soren

  公开号：US20080027104A1

  公开（公告）日：2008-01-31

  The present invention relates to 6-(4-[(benzylsulfonyl)amino]carbonyl}piperidin-1-yl)-5-cyano-2-methylnicotinic acid ethyl ester, form I and II, 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6-(4-[(苯甲基磺酰)氨基]羰基}哌啶-1-基)-5-氰基-2-甲基烟酸乙酯，I型和II型，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用途，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。