methyl 1,3-di-n-butylxanthine 7-(2,3-O-isopropylidene)-β-D-ribofuronate | 163259-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: methyl 1,3-di-n-butylxanthine 7-(2,3-O-isopropylidene)-β-D-ribofuronate
• 英文别名: methyl (3aR,4R,6S,6aS)-4-(1,3-dibutyl-2,6-dioxopurin-7-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylate
• CAS: 163259-30-1
• 化学式: C₂₂H₃₂N₄O₇
• 分子量: 464.519
• InChiKey: KJRMCMUPZFRZEH-CYJAXWMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 1,3-di-n-butylxanthine 7-(2,3-O-isopropylidene)-β-D-ribofuronate 在 甲酸 作用下， 以 甲醇 为溶剂， 反应 23.0h， 生成 N-methyl 1,3-di-n-butylxanthine 7-β-D-ribofuronamide
  参考文献：
  名称：

  Selective Ligands for Rat A3 Adenosine Receptors: Structure-Activity Relationships of 1,3-Dialkylxanthine 7-Riboside Derivatives

  摘要：

  1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase.

  DOI：

  10.1021/jm00049a021
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 在 4-二甲氨基吡啶 、 ruthenium trichloride 、 sodium periodate 、 三氯硅烷 、 氨 、 水 、 对甲苯磺酸 、 potassium nonaflate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 231.0h， 生成 methyl 1,3-di-n-butylxanthine 7-(2,3-O-isopropylidene)-β-D-ribofuronate
  参考文献：
  名称：

  Selective Ligands for Rat A3 Adenosine Receptors: Structure-Activity Relationships of 1,3-Dialkylxanthine 7-Riboside Derivatives

  摘要：

  1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase.

  DOI：

  10.1021/jm00049a021

文献信息

• Selective Ligands for Rat A3 Adenosine Receptors: Structure-Activity Relationships of 1,3-Dialkylxanthine 7-Riboside Derivatives
  作者：Hea Ok Kim、Xiao-duo Ji、Neli Melman、Mark E. Olah、Gary L. Stiles、Kenneth A. Jacobson

  DOI：10.1021/jm00049a021

  日期：1994.11

  1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase.