endo-7-<(3-cyclopentyloxy)-4-methoxyphenyl>hexahydropyrrolo<1,2-c>imidazol-3-one

• 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: endo-7-<(3-cyclopentyloxy)-4-methoxyphenyl>hexahydropyrrolo<1,2-c>imidazol-3-one
• 英文别名: (7S*,7aR*)-7-(3-cyclopentyloxy-4-methoxyphenyl)hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one；trans-7-[3-(cyclopentyloxy)-4-methoxyphenyl]hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one；(7R,7aS)-7-(3-Cyclopentyloxy-4-methoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one；(7R,7aS)-7-(3-cyclopentyloxy-4-methoxyphenyl)-1,2,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazol-3-one
• 化学式: C₁₈H₂₄N₂O₃
• 分子量: 316.4
• InChiKey: CXPNXCHISHWKQD-HUUCEWRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 sodium azide 、 三甲基溴硅烷 、 ammonium acetate 、 氢气 、 四氯化锡 、 sodium cyanoborohydride 、 三乙胺 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 丙酮 为溶剂， -94.0~75.0 ℃ 、4.05 MPa 条件下， 反应 30.0h， 生成 endo-7-<(3-cyclopentyloxy)-4-methoxyphenyl>hexahydropyrrolo<1,2-c>imidazol-3-one
  参考文献：
  名称：

  Synthesis of phosphodiesterase IVb inhibitors 2. Stereoselective synthesis of hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one and tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one derivatives

  摘要：

  从硝基乙烷、异香草醛和乙基乙烯醚出发，完成了两种高效 PDE IVb 抑制剂的全立体选择性合成。所得化合物的衍生物为六氢-3H-吡咯并[1,2-c]咪唑-3-酮和四氢-1H-吡咯并[1,2-c][1,3]噁唑-3-酮。提出的策略涉及将六元环状硝酮的硅烷化作为关键步骤，生成在 C(3) 原子上带有 CH2FG（FG = N3 或 OH）基团的 5,6-二氢-4H-1,2-噁嗪。

  DOI：

  10.1007/s11172-011-0367-5

文献信息

• Synthesis of phosphodiesterase IVb inhibitors 2. Stereoselective synthesis of hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one and tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one derivatives
  作者：P. A. Zhmurov、A. A. Tabolin、A. Yu. Sukhorukov、A. V. Lesiv、M. S. Klenov、Yu. A. Khomutova、S. L. Ioffe、V. A. Tartakovsky

  DOI：10.1007/s11172-011-0367-5

  日期：2011.11

  The total stereoselective synthesis of two highly potent phosphodiesterase IVb inhibitors from nitroethane, isovanillin, and ethyl vinyl ether was developed. The compounds obtained are the derivatives of hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one and tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one. The strategy proposed involves silylation of six-membered cyclic nitronates as a key step leading to 5,6-dihydro-4H-1,2-oxazines with the group CH2FG (FG = N3 or OH) at the C(3) atom.

  从硝基乙烷、异香草醛和乙基乙烯醚出发，完成了两种高效 PDE IVb 抑制剂的全立体选择性合成。所得化合物的衍生物为六氢-3H-吡咯并[1,2-c]咪唑-3-酮和四氢-1H-吡咯并[1,2-c][1,3]噁唑-3-酮。提出的策略涉及将六元环状硝酮的硅烷化作为关键步骤，生成在 C(3) 原子上带有 CH2FG（FG = N3 或 OH）基团的 5,6-二氢-4H-1,2-噁嗪。
• 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.
• Synthesis of PDE IV inhibitors. First asymmetric synthesis of two of GlaxoSmithKline's highly potent Rolipram analogues
  作者：Petr A. Zhmurov、Alexey Yu. Sukhorukov、Vladimir I. Chupakhin、Yulia V. Khomutova、Sema L. Ioffe、Vladimir A. Tartakovsky

  DOI：10.1039/c3ob41646a

  日期：——

  Asymmetric syntheses of two of GlaxoSmithKline's highly potent phosphodiesterase IV inhibitors CMPI 1 and CMPO 2 have been accomplished from nitroethane and simple precursors in 8 and 7 steps, respectively. The suggested synthetic strategy involves as a key stage the silylation of enantiopure six-membered cyclic nitronates. In vitro studies of PDE IVB1 inhibition revealed a significant difference in the activity of CMPI 1 and CMPO 2 enantiomers.

  葛兰素史克的两种高效磷酸二酯酶 IV 抑制剂 CMPI 1 和 CMPO 2 已分别通过 8 步和 7 步从硝基乙烷和简单前体完成不对称合成。建议的合成策略包括对映体纯六元环硝基化合物的硅烷化作为关键阶段。 PDE IVB1 抑制的体外研究表明 CMPI 1 和 CMPO 2 对映体的活性存在显着差异。