cis-3-<3-(cyclopentyloxy)-4-methoxyphenyl>-2-<methyl>pyrrolidine-1-carboxylic acid phenyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: cis-3-<3-(cyclopentyloxy)-4-methoxyphenyl>-2-<methyl>pyrrolidine-1-carboxylic acid phenyl ester
• 英文别名: phenyl (2R,3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-2-[(phenoxycarbonylamino)methyl]pyrrolidine-1-carboxylate
• 化学式: C₃₁H₃₄N₂O₆
• 分子量: 530.621
• InChiKey: MAESZLFFPHABBL-SXOMAYOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  cis-3-<3-(cyclopentyloxy)-4-methoxyphenyl>-2-<methyl>pyrrolidine-1-carboxylic acid phenyl ester 在 sodium hydride 、 苯酚 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以59%的产率得到exo-7-<(3-cyclopentyloxy)-4-methoxyphenyl>hexahydropyrrolo<1,2-c>imidazol-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：

  3-环戊氧-4-甲氧基苯甲醛 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 锂硼氢 、 sodium azide 、 sodium ethanolate 、 三乙胺 、 lithium iodide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.33h， 生成 cis-3-<3-(cyclopentyloxy)-4-methoxyphenyl>-2-<methyl>pyrrolidine-1-carboxylic acid phenyl 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