5-<3-(cyclopentyloxy)-4-methoxyphenyl>-7-nitro-4-oxoheptanoic acid methyl ester | 172604-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-<3-(cyclopentyloxy)-4-methoxyphenyl>-7-nitro-4-oxoheptanoic acid methyl ester
• 英文别名: methyl 5-(3-cyclopentyloxy-4-methoxyphenyl)-7-nitro-4-oxoheptanoate
• CAS: 172604-05-6
• 化学式: C₂₀H₂₇NO₇
• 分子量: 393.437
• InChiKey: NICIKMBIKKASPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-<3-(cyclopentyloxy)-4-methoxyphenyl>-7-nitro-4-oxoheptanoic acid methyl ester 在 镍 氢气 作用下， 以 甲醇 为溶剂， 65.0 ℃ 、551.58 kPa 条件下， 反应 6.0h， 以55%的产率得到endo-7-<3-(cyclopentyloxy)-4-methoxyphenyl>hexahydropyrrolizidin-3-one
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Analogs of 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) as Potent Inhibitors of cAMP-Specific Phosphodiesterase

  摘要：

  The synthesis and biological evaluation of cAMP-specific phosphodiesterase (PDE IV) inhibitors is described. The PDE TV inhibitor 4-(3-butoxy-4-methoxybenzyl)imidazolidin (Ro 20-1724, 2) was used as a template from which to design a set of rigid oxazolidinones, imidazolidinones, and pyrrolizidinones that mimic Ro 20-1724 but differ in the orientation of the carbonyl group. The endo isomer of each of these heterocycles was more potent than the exo isomer in an enzyme inhibition assay and a cellular assay, which measured TNF alpha secretion from activated human peripheral blood monocytes (HPBM). Imidazolidinone 4a inhibited human PDE I with a K-i of 27 nM and TNF alpha secretion from HPBM with an IC50 of 290 nM. By comparison, Ro 20-1724 is significantly less active in these assays with activities of 1930 and 1800 nM, respectively.

  DOI：

  10.1021/jm00024a012
• 作为产物：
  描述：

  2-(cyclopentyloxy)-1-methoxy-4-<1-(tributylstannyl)vinyl>benzene 在 1,1,2,3-四甲基胍 、 trans-benzyl(chloro)bis(triphenylphosphine)palladium(II) 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 5-<3-(cyclopentyloxy)-4-methoxyphenyl>-7-nitro-4-oxoheptanoic acid methyl ester
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Analogs of 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) as Potent Inhibitors of cAMP-Specific Phosphodiesterase

  摘要：

  The synthesis and biological evaluation of cAMP-specific phosphodiesterase (PDE IV) inhibitors is described. The PDE TV inhibitor 4-(3-butoxy-4-methoxybenzyl)imidazolidin (Ro 20-1724, 2) was used as a template from which to design a set of rigid oxazolidinones, imidazolidinones, and pyrrolizidinones that mimic Ro 20-1724 but differ in the orientation of the carbonyl group. The endo isomer of each of these heterocycles was more potent than the exo isomer in an enzyme inhibition assay and a cellular assay, which measured TNF alpha secretion from activated human peripheral blood monocytes (HPBM). Imidazolidinone 4a inhibited human PDE I with a K-i of 27 nM and TNF alpha secretion from HPBM with an IC50 of 290 nM. By comparison, Ro 20-1724 is significantly less active in these assays with activities of 1930 and 1800 nM, respectively.

  DOI：

  10.1021/jm00024a012

文献信息

• Design and Synthesis of Conformationally Constrained Analogs of 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) as Potent Inhibitors of cAMP-Specific Phosphodiesterase
  作者：Marcus F. Brackeen、Jeffrey A. Stafford、David J. Cowan、Peter J. Brown、Paul L. Domanico、Paul L. Feldman、Dudley Rose、Alan B. Strickland、James M. Veal、Margrith Verghese

  DOI：10.1021/jm00024a012

  日期：1995.11

  The synthesis and biological evaluation of cAMP-specific phosphodiesterase (PDE IV) inhibitors is described. The PDE TV inhibitor 4-(3-butoxy-4-methoxybenzyl)imidazolidin (Ro 20-1724, 2) was used as a template from which to design a set of rigid oxazolidinones, imidazolidinones, and pyrrolizidinones that mimic Ro 20-1724 but differ in the orientation of the carbonyl group. The endo isomer of each of these heterocycles was more potent than the exo isomer in an enzyme inhibition assay and a cellular assay, which measured TNF alpha secretion from activated human peripheral blood monocytes (HPBM). Imidazolidinone 4a inhibited human PDE I with a K-i of 27 nM and TNF alpha secretion from HPBM with an IC50 of 290 nM. By comparison, Ro 20-1724 is significantly less active in these assays with activities of 1930 and 1800 nM, respectively.