(1S,3S)-1-(9-adenenyl)-3-(N-hydroxycarbamoyl)-4-cyclopentene | 426226-47-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1S,3S)-1-(9-adenenyl)-3-(N-hydroxycarbamoyl)-4-cyclopentene
• 英文别名: (1R,3R)-4-(6-Amino-purin-9-yl)-cyclopent-2-enecarboxylic acid hydroxyamide；(1S,4S)-4-(6-aminopurin-9-yl)-N-hydroxycyclopent-2-ene-1-carboxamide
• CAS: 426226-47-3
• 化学式: C₁₁H₁₂N₆O₂
• 分子量: 260.255
• InChiKey: CJIKFXCNDDQKNZ-RNFRBKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,3S)-1-(9-adenenyl)-3-(N-hydroxycarbamoyl)-4-cyclopentene 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 20.0h， 生成 (1R,3R)-3-(6-amino-9H-purin-9-yl)-N-hydroxycyclopentanecarboxamide
  参考文献：
  名称：

  Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists

  摘要：

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.

  DOI：

  10.1021/jm0205604
• 作为产物：
  描述：

  (1R,4S)-4-氨基环戊-2-烯甲酸 在 氢氧化钾 、 sodium azide 、 甲烷磺酸 、 盐酸羟胺 、 三乙胺 、 乙酰氯 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 33.91h， 生成 (1S,3S)-1-(9-adenenyl)-3-(N-hydroxycarbamoyl)-4-cyclopentene
  参考文献：
  名称：

  Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists

  摘要：

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.

  DOI：

  10.1021/jm0205604

文献信息

• Regulation of type 5 adenylyl cyclase for treatment of neurodegenerative and cardiac diseases
  申请人：Vatner F. Stephen

  公开号：US20060252774A1

  公开（公告）日：2006-11-09

  The invention concerns pharmaceutical compositions that contain a compound or compounds that can effectively regulate the activity of Type 5 Adenylyl Cyclase and methods for treatment of neurological diseases and disorders, as well as motor function loss therefrom, as well as treatment for cardiac conditions and diseases including conditions characterized by abnormal heart rate.

  这项发明涉及含有一种或多种能够有效调节第5型腺苷酸环化酶活性的化合物的药物组合物，以及治疗神经系统疾病和障碍、以及由此引起的运动功能丧失的方法，以及用于治疗心脏疾病和疾病的方法，包括以异常心率为特征的情况。