5'-deoxy-N⁶-(3-iodobenzyl)-5'-(isopropylthio)adenosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-deoxy-N⁶-(3-iodobenzyl)-5'-(isopropylthio)adenosine
• 英文别名: (2R,3R,4S,5S)-2-[6-[(3-iodophenyl)methylamino]purin-9-yl]-5-(propan-2-ylsulfanylmethyl)oxolane-3,4-diol
• 化学式: C₂₀H₂₄IN₅O₃S
• 分子量: 541.413
• InChiKey: IWEPXNNUQCOTQE-WVSUBDOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6-氯嘌呤核苷 在 吡啶 、 sodium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 5'-deoxy-N⁶-(3-iodobenzyl)-5'-(isopropylthio)adenosine
  参考文献：
  名称：

  N⁶,5‘-Disubstituted Adenosine Derivatives as Partial Agonists for the Human Adenosine A₃ Receptor

  摘要：

  5'-(Alkylthio)-substituted analogues of N-6-benzyl- and N-6-(3-iodobenzyl)adenosine were synthesized in 37-61% overall yields. The affinities of these compounds for the adenosine A(1), A(2A), and A(3) receptors were determined using rat brain cortex, rat brain striata, and stably transfected human A(3) receptors in HEK 293 cells, respectively. The compounds proved to be selective for the adenosine A(3) receptor and displayed affinities in the nanomolar range. Compounds 8, 10, and 11 had the highest affinities for the A(3) receptor with K-i values ranging from 8.8 to 27.7 nM. In the N-6-benzyl series, compound 4 (LUF 5403), with a 5'-methylthio group, maintained a reasonable affinity and had the highest selectivity for the A(3) receptor. Compound 12 (LUF 5411), with an N-6-(3-iodobenzyl) group and a 5'-(n-propylthio) substituent, had the highest A(3) selectivity of all of the compounds and also displayed high affinity for this receptor (K-i = 44.3 nM). The compounds were also evaluated for their ability to stimulate [S-35]GTP gamma[S] binding in cell membranes expressing the human adenosine A(3) receptor. It appeared that the N-6,5'-disubstituted adenosine derivatives behaved as partial agonists. Compounds 2, 4, 8, and 10 had the highest intrinsic activities. Additionally, when tested in a cAMP assay, these compounds also behaved as partial agonists.

  DOI：

  10.1021/jm981090+

文献信息

• <i>N</i>⁶,5‘-Disubstituted Adenosine Derivatives as Partial Agonists for the Human Adenosine A₃ Receptor
  作者：Erica W. van Tilburg、Jacobien von Frijtag Drabbe Künzel、Miriam de Groote、Roel C. Vollinga、Anna Lorenzen、Ad P. IJzerman

  DOI：10.1021/jm981090+

  日期：1999.4.22

  5'-(Alkylthio)-substituted analogues of N-6-benzyl- and N-6-(3-iodobenzyl)adenosine were synthesized in 37-61% overall yields. The affinities of these compounds for the adenosine A(1), A(2A), and A(3) receptors were determined using rat brain cortex, rat brain striata, and stably transfected human A(3) receptors in HEK 293 cells, respectively. The compounds proved to be selective for the adenosine A(3) receptor and displayed affinities in the nanomolar range. Compounds 8, 10, and 11 had the highest affinities for the A(3) receptor with K-i values ranging from 8.8 to 27.7 nM. In the N-6-benzyl series, compound 4 (LUF 5403), with a 5'-methylthio group, maintained a reasonable affinity and had the highest selectivity for the A(3) receptor. Compound 12 (LUF 5411), with an N-6-(3-iodobenzyl) group and a 5'-(n-propylthio) substituent, had the highest A(3) selectivity of all of the compounds and also displayed high affinity for this receptor (K-i = 44.3 nM). The compounds were also evaluated for their ability to stimulate [S-35]GTP gamma[S] binding in cell membranes expressing the human adenosine A(3) receptor. It appeared that the N-6,5'-disubstituted adenosine derivatives behaved as partial agonists. Compounds 2, 4, 8, and 10 had the highest intrinsic activities. Additionally, when tested in a cAMP assay, these compounds also behaved as partial agonists.