2-amino-4-(benzo[1,3]dioxo-5-yl)-6-mercaptopyridine-3,5-dicarbonitrile | 467237-85-0

• 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
• 英文名称: 2-amino-4-(benzo[1,3]dioxo-5-yl)-6-mercaptopyridine-3,5-dicarbonitrile
• 英文别名: 2-amino-4-(benzo[d][1,3]dioxol-5-yl)-6-mercaptopyridine-3,5-dicarbonitrile；2-Amino-4-(1,3-benzodioxol-5-yl)-6-sulfanyl-3,5-pyridinedicarbonitrile；2-amino-4-(1,3-benzodioxol-5-yl)-6-sulfanylidene-1H-pyridine-3,5-dicarbonitrile
• CAS: 467237-85-0
• 化学式: C₁₄H₈N₄O₂S
• 分子量: 296.309
• InChiKey: AWXNVYCMMANNOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-4-(benzo[1,3]dioxo-5-yl)-6-mercaptopyridine-3,5-dicarbonitrile 、 4-氯苯基-2-(4-氯苯基)-1,3-噻唑 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到2-Amino-4-(1,3-benzodioxol-5-yl)-6-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methylsulfanyl]pyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  Structure-kinetics relationships of Capadenoson derivatives as adenosine A 1 receptor agonists

  摘要：

  We report the synthesis and biological evaluation of new derivatives of Capadenoson, a former drug candidate that was previously advanced to phase Ha clinical trials. 19 of the 20 ligands show an affinity below 100 nM at the human adenosine A(1) receptor (hA(1)AR) and display a wide range of residence times at this target (from approx. 5 min (compound 10) up to 132 min (compound 5)). Structure-affinity and structure-kinetics relationships were established, and computational studies of a homology model of the hA(1)AR revealed crucial interactions for both the affinity and dissociation kinetics of this family of ligands. These results were also combined with global metrics (Ligand Efficiency, cLogP), showing the importance of binding kinetics as an additional way to better select a drug candidate amongst seemingly similar leads. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.07.023
• 作为产物：
  描述：

  (苯并[3,4-d]1,3-二氧杂烷-5-亚甲基)甲烷-1,1-二甲腈 在 sodium sulfide 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-amino-4-(benzo[1,3]dioxo-5-yl)-6-mercaptopyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  发现高效腺苷 A1 受体激动剂：靶向正电子发射断层扫描探针

  摘要：

  用于正电子发射断层扫描 (PET) 的腺苷受体 (AR) 放射性示踪剂提供了关于AR 在中枢神经系统 (CNS)中的体内生物分布的知识，这对各种神经精神疾病具有治疗意义。此外，仍然缺乏能够成像不同生理和病理条件下内源性腺苷水平变化的放射性配体。在啮齿动物 PET 研究中，已知拮抗剂腺苷 A 1受体 (A 1 R) 放射性示踪剂 [ 11 C]MDPX 的结合未能被升高的内源性腺苷抑制。由于大多数已知的 AR PET 放射性示踪剂都是拮抗剂，我们建议 A 1R 激动剂放射性配体可能对测量内源性腺苷浓度的变化具有更高的灵敏度。在此，我们报告了我们在开发用于 PET 的完全激动剂腺苷 A 1放射性配体方面的最新发现。基于 3,5-二氰基吡啶模板，设计和合成了 16 种新衍生物以优化结合亲和力和功能活性，从而产生了两种具有单位数纳摩尔亲和力和良好亚型选择性的完全激动剂（化合物27和29 ）（A 1

  DOI：

  10.1021/acschemneuro.1c00397

文献信息

• Design and pharmacological profile of a novel covalent partial agonist for the adenosine A1 receptor
  作者：Xue Yang、Majlen A. Dilweg、Dion Osemwengie、Lindsey Burggraaff、Daan van der Es、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1016/j.bcp.2020.114144

  日期：2020.10

  Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. Accordingly, the design and profiling of novel hA1AR partial agonists has become an

  与完全激动剂相比，G蛋白偶联受体（GPCR）的部分激动剂为新型药物治疗提供了机会，具有更高的靶标安全性。对于人类腺苷A1受体（hA1AR），这导致了Capadenoson的发现，该药物已进入IIa期用于心力衰竭的临床试验。因此，新型hA1AR部分激动剂的设计和分析已成为重要的研究重点。在这项研究中，我们报告LUF7746，一种带有亲电性氟磺酰基部分的卡帕德森衍生物，作为不可逆结合的hA1AR调节剂。同时，在我们的研究中，设计了带有甲基磺酰基部分的非反应性配体LUF7747作为对照探针。在放射性配体结合试验中，LUF7746的表观亲和力随着预孵育时间的延长而增加到纳摩尔范围，提示共价结合水平随时间增加。此外，与参考的完全激动剂CPA相比，LUF7746在hA1AR介导的G蛋白活化分析中是部分激动剂，并且对拮抗剂/反向激动剂的阻滞具有抵抗力。基于计算机结构的对接研究与hA1AR的定点诱变相结合，证明氨基酸Y2717
• Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines with adenosine receptor-binding activity and their use cardiovascular preparations
  申请人：——

  公开号：US20040102626A1

  公开（公告）日：2004-05-27

  The invention relates to the compounds of formula (I), to a method for producing them and to their use as medicaments. 1

  该发明涉及式（I）化合物，其制备方法以及它们作为药物的用途。
• Substituted 2-thio-3,5-dicyano-4-phenyl-6-aminopyridines with adenosine receptor-binding activity and their use as cardiovascular preparations
  申请人：Bayer Aktiengesellschaft

  公开号：US07078417B2

  公开（公告）日：2006-07-18

  This application relates to pyridine derivatives having the general structure in which the several variables are as defined in the specification and claims, and to a process for preparing these compounds, a pharmacutical composition containing such compounds, and a method for using these materials for treatment of stable and unstable angina pectoris and atrial fibrillation.

  本申请涉及具有一般结构的吡啶衍生物，其中几个变量如规范和要求中所定义，并且涉及制备这些化合物的过程，包含这些化合物的药物组合物，以及使用这些材料治疗稳定和不稳定型心绞痛和心房颤动的方法。
• A Series of Ligands Displaying a Remarkable Agonistic−Antagonistic Profile at the Adenosine A₁ Receptor
  作者：Lisa C. W. Chang、Jacobien K. von Frijtag Drabbe Künzel、Thea Mulder-Krieger、Ronald F. Spanjersberg、Sophie F. Roerink、Gijs van den Hout、Margot W. Beukers、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm049597+

  日期：2005.3.1

  Adenosine receptor agonists are usually variations of the natural ligand, adenosine. The ribose moiety in the ligand has previously been shown to be of great importance for the agonistic effects of the compound. In this paper, we present a series of nonadenosine ligands selective for the adenosine A(1) receptor with an extraordinary pharmacological profile. 2-Amino-4-benzo[1,3]dioxol-5-yl-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile (70, LUF 5853) shows full agonistic behavior comparable with the reference compound CPA, while also displaying comparable receptor binding affinity (K-i = 11 nM). In contrast, compound 58 (2-amino-4-(3-trifluoromethylphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5948) has a binding affinity of 14 nM and acts as an inverse agonist. Also present within this same series are compounds that show neutral antagonism of the adenosine A(1) receptor, for example compound 65 (2-amino-4-(4-difluoromethoxyphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5826).
• A Chemical Biological Approach to Study G Protein-Coupled Receptors: Labeling the Adenosine A₁ Receptor Using an Electrophilic Covalent Probe
  作者：Bert L. H. Beerkens、Çağla Koç、Rongfang Liu、Bogdan I. Florea、Sylvia E. Le Dévédec、Laura H. Heitman、Adriaan P. IJzerman、Daan van der Es

  DOI：10.1021/acschembio.2c00589

  日期：2022.11.18