[(1S,4S)-4-(6-Amino-purin-9-yl)-cyclopent-2-enyl]-acetic acid methyl ester

• 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,4S)-4-(6-Amino-purin-9-yl)-cyclopent-2-enyl]-acetic acid methyl ester
• 英文别名: methyl 2-[(1S,4S)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]acetate
• 化学式: C₁₃H₁₅N₅O₂
• 分子量: 273.294
• InChiKey: IZQJUZPJSVGAAA-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(1S,4S)-4-(6-Amino-purin-9-yl)-cyclopent-2-enyl]-acetic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 (1S,3S)-1-(9-adenenyl)-3-carboxymethyl-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
• 作为产物：
  描述：

  2-环戊烯-1-醇,4-[[(1,1-二甲基乙基)二甲基甲硅烷基]氧代]-,(1R,4S)- 在 甲醇 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 sodium methylate 、 sodium hydride 、 对甲苯磺酸 、 甲基磺酰氯 、 N,N-二异丙基乙胺 、 三苯基膦 、 lithium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 126.25h， 生成 [(1S,4S)-4-(6-Amino-purin-9-yl)-cyclopent-2-enyl]-acetic acid methyl ester
  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

• Synthesis of cyclopentenyl carbanucleosides via palladium(0) catalysed reactions
  作者：H. Kapeller、C. Marschner、M. Weißenbacher、H. Grieng

  DOI：10.1016/s0040-4020(97)10380-5

  日期：1998.2

  have been treated with sodium salts and aluminum amides of pyrimidines, purines and methyl 1H-1,2,4-triazole-3-carboxylate with a catalyst formed from bis(dibenzylideneacetone)palladium(0) and triisopropyl phosphite to give the corresponding carbanucleosides in good to excellent yields. This method was also applied for a synthesis of carbovir (31).

  用嘧啶，嘌呤和1 H -1,2,4-4-三唑-3-羧酸甲酯的钠盐和铝酰胺处理4-乙酰氧基环戊-2-烯基甲基羧酸甲酯（2）和相应的碳酸酯3双（二亚苄基丙酮）钯（0）​​和亚磷酸三异丙酯，以良好或优异的收率得到相应的碳核苷。该方法也适用于卡波韦的合成（31）。