(3aR,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester | 205171-19-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (3aR,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester
• 英文别名: ethyl (3aR,4R,6S,6aR)-4-(6-aminopurin-9-yl)-2,2,3a-trimethyl-6,6a-dihydro-4H-furo[3,4-d][1,3]dioxole-6-carboxylate
• CAS: 205171-19-3
• 化学式: C₁₆H₂₁N₅O₅
• 分子量: 363.373
• InChiKey: QPTWOALFNMFFKN-KBNRHUEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3aR,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester 在 盐酸 作用下， 反应 6.0h， 生成 (2S,3R,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-4-methyl-tetrahydro-furan-2-carboxylic acid ethylamide
  参考文献：
  名称：

  2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies

  摘要：

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

  DOI：

  10.1021/jm9707737
• 作为产物：
  描述：

  6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 氢氧化钾 、 potassium permanganate 、 氯化亚砜 、 氨 、 对甲苯磺酸 、 2,2-二甲氧基丙烷 作用下， 反应 31.0h， 生成 (3aR,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies

  摘要：

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

  DOI：

  10.1021/jm9707737

文献信息

• 2‘-<i>C</i>-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies
  作者：Palmarisa Franchetti、Loredana Cappellacci、Stefano Marchetti、Letizia Trincavelli、Claudia Martini、Maria R. Mazzoni、Antonio Lucacchini、Mario Grifantini

  DOI：10.1021/jm9707737

  日期：1998.5.1

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.