3'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)propanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)propanamide
• 英文别名: 3-(4-Amino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylsulfanyl)-propionamide；3-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl)sulfanylpropanamide
• 化学式: C₁₄H₁₄N₆OS
• 分子量: 314.371
• InChiKey: AFXKLUCTBPZBAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-phenylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dithione 在 吡啶 、 sodium hydroxide 、 氨 作用下， 以 乙醇 为溶剂， 反应 75.5h， 生成 3'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)propanamide
  参考文献：
  名称：

  1-Phenylpyrazolo[3,4-d]pyrimidines as adenosine antagonists: the effects of substituents at C4 and C6

  摘要：

  Forty-two 1-phenyl-pyrazolo[3,4-d]pyrimidines substituted at C6 with thioethers containing distal amide substituents and substituted at C4 with thiol, thiomethyl or amino were synthesized and tested for adenosine A(1) and A(2a) receptor binding. Compared with a thiol at C4, both S-methylation and conversion to an amino resulted in increased affinity at both receptors with the C4 amino compounds having the highest affinity. The C-4 region of the receptor consists of an alkyl pocket containing a hydrogen-bonding site. The study established that for high affinity at both the A(1) and A(2a) adenosine receptors the distal amide should be separated from the C6 thiol by only one carbon. In this study, 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)- N-ethyl-ethanamide (4b) had the highest affinity at the A(1) receptor with a K-i of 12.1 nM while 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)ethanamide (4a) had the highest affinity at the A(2a) receptor with a K-i of 44.9 nM. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(96)00240-4

文献信息

• COMPOUNDS FOR THE TREATMENT OF AURICULAR FIBRILLATION
  申请人：Proyecto de Biomedicina Cima, S.L.

  公开号：EP1949903A2

  公开（公告）日：2008-07-30

  Adenosine A2A receptor antagonists are useful for the preparation of medicaments against atrial fibrillation in mammals, including humans. It has been found that the adenosine A2A receptor is present in human atrial cardiomyocytes and participates in the pathological mechanisms underlying atrial fibrillation. An advantage of using A2A antagonists over other agents known in the art is that the A2A antagonists specifically target patients with atrial fibrillation.

  腺苷 A2A 受体拮抗剂可用于制备防治哺乳动物（包括人类）心房颤动的药物。研究发现，腺苷 A2A 受体存在于人类心房心肌细胞中，并参与心房颤动的病理机制。与本领域已知的其他药物相比，使用 A2A 拮抗剂的优势在于 A2A 拮抗剂专门针对心房颤动患者。
• SELECTIVE A2A RECEPTOR ANTAGONISTS FOR THE TREATMENT OF AURICULAR FIBRILLATION
  申请人：Proyecto de Biomedicina Cima, S.L.

  公开号：EP1949903B1

  公开（公告）日：2012-04-18
• US8012973B2
  申请人：——

  公开号：US8012973B2

  公开（公告）日：2011-09-06
• [EN] COMPOUNDS FOR THE TREATMENT OF AURICULAR FIBRILLATION<br/>[ES] COMPUESTOS PARA EL TRATAMIENTO DE LA FIBRILACIÓN AURICULAR<br/>[FR] COMPOSES SERVANT A TRAITER LA FIBRILLATION AURICULAIRE
  申请人：UNIV BARCELONA

  公开号：WO2007045705A2

  公开（公告）日：2007-04-26

  [EN] The invention relates to antagonists of the adenosine A_2A receptor, which can be used for the preparation of medicaments for auricular fibrillation in mammals, including humans. It has been found that the A_2A adenosine receptor is present in human auricular cardiomyocytes and involved in the basic pathological mechanisms of auricular fibrillation. The use of A_2A antagonists is advantageous over other known agents in that A_2A antagonists are directed specifically to patients with auricular fibrillation.
  [FR] Les antagonistes du récepteur d'adénosine A2A selon l'invention sont utiles dans la préparation de médicaments contre la fibrillation auriculaire chez les mammifères, y compris chez l'homme. On a découvert que le récepteur d'adénosine A2a est présent dans les cardiomyocytes auriculaires humains et qu'il participe aux mécanismes pathologiques fondamentaux de la fibrillation auriculaire. Il est particulièrement avantageux d'utiliser des antagonistes A2A plutôt que d'autres agents déjà connus dans la technique car ils s'adressent spécifiquement à des patients atteints d'une fibrillation auriculaire.
  [ES] Los antagonistas del receptor de adenosina A_2A son útiles para la preparación de medicamentos contra la fibrilación auricular en mamíferos, incluyendo el hombre. Se ha encontrado que el receptor de adenosina A_2A es presente en los cardiomiocitos auriculares humanos y participa en los mecanismos patológicos fundamentales de la fibrilación auricular. Una ventaja de utilizar antagonistas A_2A sobre otros agentes conocidos en la técnica es que los antagonistas A_2A van dirigidos específicamente a pacientes con fibrilación auricular.
• 1-Phenylpyrazolo[3,4-d]pyrimidines as adenosine antagonists: the effects of substituents at C4 and C6
  作者：Mary Chebib、Ronald J. Quinn

  DOI：10.1016/s0968-0896(96)00240-4

  日期：1997.2

  Forty-two 1-phenyl-pyrazolo[3,4-d]pyrimidines substituted at C6 with thioethers containing distal amide substituents and substituted at C4 with thiol, thiomethyl or amino were synthesized and tested for adenosine A(1) and A(2a) receptor binding. Compared with a thiol at C4, both S-methylation and conversion to an amino resulted in increased affinity at both receptors with the C4 amino compounds having the highest affinity. The C-4 region of the receptor consists of an alkyl pocket containing a hydrogen-bonding site. The study established that for high affinity at both the A(1) and A(2a) adenosine receptors the distal amide should be separated from the C6 thiol by only one carbon. In this study, 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)- N-ethyl-ethanamide (4b) had the highest affinity at the A(1) receptor with a K-i of 12.1 nM while 2'-(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-ylthio)ethanamide (4a) had the highest affinity at the A(2a) receptor with a K-i of 44.9 nM. (C) 1997, Elsevier Science Ltd.