4-{1-[6-Amino-3-(3-cyclopentyloxy-4-methoxy-benzyl)-3H-purin-8-yl]-1-methyl-ethoxymethyl}-benzoic acid methyl ester | 847978-31-8

• 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: 4-{1-[6-Amino-3-(3-cyclopentyloxy-4-methoxy-benzyl)-3H-purin-8-yl]-1-methyl-ethoxymethyl}-benzoic acid methyl ester
• 英文别名: methyl 4-[2-[6-amino-3-[(3-cyclopentyloxy-4-methoxyphenyl)methyl]purin-8-yl]propan-2-yloxymethyl]benzoate
• CAS: 847978-31-8
• 化学式: C₃₀H₃₅N₅O₅
• 分子量: 545.638
• InChiKey: IESKAFPEEMSDOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.98
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  123.61
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-{1-[6-Amino-3-(3-cyclopentyloxy-4-methoxy-benzyl)-3H-purin-8-yl]-1-methyl-ethoxymethyl}-benzoic acid methyl ester 在 氨 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以75%的产率得到4-{1-[6-Amino-3-(3-cyclopentyloxy-4-methoxy-benzyl)-3H-purin-8-yl]-1-methyl-ethoxymethyl}-benzamide
  参考文献：
  名称：

  8-Substituted Analogues of 3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl- adenine: Highly Potent and Selective PDE4 Inhibitors

  摘要：

  3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.

  DOI：

  10.1021/jm030603w
• 作为产物：
  描述：

  4-(氯甲基)-2-(环戊氧基)-1-甲氧基苯 在 potassium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-{1-[6-Amino-3-(3-cyclopentyloxy-4-methoxy-benzyl)-3H-purin-8-yl]-1-methyl-ethoxymethyl}-benzoic acid methyl ester
  参考文献：
  名称：

  8-Substituted Analogues of 3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl- adenine: Highly Potent and Selective PDE4 Inhibitors

  摘要：

  3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.

  DOI：

  10.1021/jm030603w

文献信息

• 8-Substituted Analogues of 3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl- adenine: Highly Potent and Selective PDE4 Inhibitors
  作者：John W. F. Whitehead、Gary P. Lee、Parviz Gharagozloo、Peter Hofer、André Gehrig、Peter Wintergerst、Donald Smyth、William McCoull、Mohamed Hachicha、Aniket Patel、Donald J. Kyle

  DOI：10.1021/jm030603w

  日期：2005.2.1

  3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8-[(benzyloxy)methyl]-substituted analogues, with potencies in the range 10-300 nM. In addition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl derivative 5v, which showed 6-10 nM potency at PDE4B, D3, and D5 and a 20- to 200-fold selectivity over A and D2, respectively.