N⁶-[(R)-tetrahydrofuran-3-yl]-9-(2-C-methyl-β-D-ribofuranosyl)adenine

• 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: N⁶-[(R)-tetrahydrofuran-3-yl]-9-(2-C-methyl-β-D-ribofuranosyl)adenine
• 英文别名: 2'-Me-Tecadenoson；(2R,3R,4R,5R)-5-(hydroxymethyl)-3-methyl-2-[6-[[(3R)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol
• 化学式: C₁₅H₂₁N₅O₅
• 分子量: 351.362
• InChiKey: BPEIIXZHZSYVFH-LVSZHXFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-[(R)-tetrahydrofuran-3-yl]-9-(2-C-methyl-β-D-ribofuranosyl)adenine 、 2,2-二甲氧基丙烷 在 camphor-10-sulfonic acid 作用下， 以 丙酮 为溶剂， 反应 4.5h， 以76%的产率得到N6-[(R)-tetrahydrofuran-3-yl]-9-(2-C-methyl-2,3-O-isopropylidene-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: Affinity, efficacy, and selectivity for A1 receptor from different species

  摘要：

  A series of 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-C-methyl analogues of the A, adenosine receptor (AIAR) full agonists N-6-cyclopentyladenosine (CPA), 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N-6-cyclopentylamino series, the 5'-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N-6-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine AIAR. The 5'-methylthionocarbamoyl derivative of 2'-Me-CCPA showed the best affinity at porcine AIAR with a K-i value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at AIAR and very low affinity at the other subtypes (A(2A), A(2B), and A(3) compared to the corresponding N-6-cyclopentyl analogues. The 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-Me-CCPA 3, 4, 7 and tecadenoson derivative 12 were found to be partial A, agonists at the porcine receptor. Docking studies explained the lower affinity of N-6-3-(R)-tetrahydrofuranyl-substituted compounds at bovine AIAR compared to that of N-6-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavorable electrostatic interactions with the CO oxygen of Asn254. The low binding affinity of the 2'-C-methyl-N-6-3-(R)-tetrahydrofuranyl adenosine analogues at human AIAR may be ascribed to the presence of unfavorable interactions between the hydrophilic tetrahydrofuranyl ring and the surrounding hydrophobic residues Leu250 (TM6) and Ile274 (TM7). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.035
• 作为产物：
  描述：

  在 甲醇 、 sodium methylate 作用下， 反应 0.67h， 生成 N⁶-[(R)-tetrahydrofuran-3-yl]-9-(2-C-methyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: Affinity, efficacy, and selectivity for A1 receptor from different species

  摘要：

  A series of 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-C-methyl analogues of the A, adenosine receptor (AIAR) full agonists N-6-cyclopentyladenosine (CPA), 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N-6-cyclopentylamino series, the 5'-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N-6-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine AIAR. The 5'-methylthionocarbamoyl derivative of 2'-Me-CCPA showed the best affinity at porcine AIAR with a K-i value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at AIAR and very low affinity at the other subtypes (A(2A), A(2B), and A(3) compared to the corresponding N-6-cyclopentyl analogues. The 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-Me-CCPA 3, 4, 7 and tecadenoson derivative 12 were found to be partial A, agonists at the porcine receptor. Docking studies explained the lower affinity of N-6-3-(R)-tetrahydrofuranyl-substituted compounds at bovine AIAR compared to that of N-6-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavorable electrostatic interactions with the CO oxygen of Asn254. The low binding affinity of the 2'-C-methyl-N-6-3-(R)-tetrahydrofuranyl adenosine analogues at human AIAR may be ascribed to the presence of unfavorable interactions between the hydrophilic tetrahydrofuranyl ring and the surrounding hydrophobic residues Leu250 (TM6) and Ile274 (TM7). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.035

文献信息

• 5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: Affinity, efficacy, and selectivity for A1 receptor from different species
  作者：Loredana Cappellacci、Palmarisa Franchetti、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Barbara Costa、Francesca Spinetti、Claudia Martini、Karl-Norbert Klotz、Mario Grifantini

  DOI：10.1016/j.bmc.2007.09.035

  日期：2008.1

  A series of 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-C-methyl analogues of the A, adenosine receptor (AIAR) full agonists N-6-cyclopentyladenosine (CPA), 2-chloro-N-6-cyclopentyladenosine (CCPA), N-6-[3-(R)-tetrahydrofuranyl]adenosine (tecadenoson), and 2-chloro analogue (2-Cl-tecadenoson) was synthesized and evaluated for their affinity for adenosine receptor subtypes from bovine, porcine, and human species. In the N-6-cyclopentylamino series, the 5'-substituted derivatives showed a reduced affinity at the bovine A(1)AR compared to the parent compounds; however, the selectivity for A(1) versus A(2A) receptor was retained or increased. The corresponding N-6-3-(R)-tetrahydrofuranylamino analogues displayed a very low affinity toward the bovine AIAR. The 5'-methylthionocarbamoyl derivative of 2'-Me-CCPA showed the best affinity at porcine AIAR with a K-i value of 13 nM. At human AR subtypes tecadenoson derivatives showed 2.3- to 5-fold lower affinity at AIAR and very low affinity at the other subtypes (A(2A), A(2B), and A(3) compared to the corresponding N-6-cyclopentyl analogues. The 5'-carbamoyl and 5'-thionocarbamoyl derivatives of 2'-Me-CCPA 3, 4, 7 and tecadenoson derivative 12 were found to be partial A, agonists at the porcine receptor. Docking studies explained the lower affinity of N-6-3-(R)-tetrahydrofuranyl-substituted compounds at bovine AIAR compared to that of N-6-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavorable electrostatic interactions with the CO oxygen of Asn254. The low binding affinity of the 2'-C-methyl-N-6-3-(R)-tetrahydrofuranyl adenosine analogues at human AIAR may be ascribed to the presence of unfavorable interactions between the hydrophilic tetrahydrofuranyl ring and the surrounding hydrophobic residues Leu250 (TM6) and Ile274 (TM7). (c) 2007 Elsevier Ltd. All rights reserved.