1-ureido-3-(3-cyclopentoxy-4-methoxyphenyl)pyrrolidine

• 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: 1-ureido-3-(3-cyclopentoxy-4-methoxyphenyl)pyrrolidine
• 英文别名: 3-(3-Cyclopentyloxy-4-methoxyphenyl)pyrrolidine-1-carboxamide
• 化学式: C₁₇H₂₄N₂O₃
• 分子量: 304.389
• InChiKey: DXZXLXTURIDBSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  三甲基硅基异氰酸酯 、 3-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidine 在 4-二甲氨基吡啶 、 磷酸 作用下， 生成 1-ureido-3-(3-cyclopentoxy-4-methoxyphenyl)pyrrolidine
  参考文献：
  名称：

  Phosphodiesterase Type IV Inhibition. Structure-Activity Relationships of 1,3-Disubstituted Pyrrolidines

  摘要：

  The synthesis of 1,3-disubstituted pyrrolidines 2 and their activities as type IV phosphodiesterase (PDE) inhibitors are described. Various groups were appended to the nitrogen of the pyrrolidine nucleus to enable structure-activity relationships to be assessed. Groups which render the pyrrolidine nitrogen of 2 nonbasic yielded potent PDE-IV inhibitors. Analogs of amides, carbamates, and ureas of 2 were synthesized to determine the effects that substitution on these functional groups had on PDE-IV inhibitor potency. The structural requirements for PDE-IV inhibitor potency differed among the three classes. A representative amide, carbamate, and urea (2c,d,h) were shown to be >50-fold selective for inhibiting PDE-IV versus representative PDEs from families I-III and V. Furthermore, these same three inhibitors demonstrated potent functional activity (IC50 < 1 mu M) by inhibiting tumor necrosis factor-alpha (TNF-alpha) release from lipopolysaccharide (LPS)-activated purified human peripheral blood monocytes and mouse peritoneal macrophages. These compounds were also tested orally in LPS-injected mice and demonstrated dose-dependent inhibition of serum TNF-alpha levels.

  DOI：

  10.1021/jm00009a011

文献信息

• Synergistic combination
  申请人：Nycomed GmbH

  公开号：EP2193808A1

  公开（公告）日：2010-06-09

  The invention relates to the combined administration of PDE inhibitors and β2 adrenoceptor agonists for the treatment of respiratory tract disorders.

  本发明涉及联合使用 PDE 抑制剂和 β2 肾上腺素受体激动剂治疗呼吸道疾病。
• [EN] NEW COMBINATION<br/>[FR] NOUVELLE COMBINAISON
  申请人：ALTANA PHARMA AG

  公开号：WO2003024488A2

  公开（公告）日：2003-03-27

  The invention relates to the combined administration of PDE4 or PDE3/4 inhibitors and leukotriene receptor antagonists for the treatment of respiratory tract disorders.
• [EN] PDE4 AND PDE3/4 INHIBITORS FOR USE IN THE TREATMENT OF CACHEXIA<br/>[FR] INHIBITEURS DE PDE4 ET PDE3/4 QUE L'ON UTILISE DANS LE TRAITEMENT DE LA CACHEXIE
  申请人：ALTANA PHARMA AG

  公开号：WO2004047817A1

  公开（公告）日：2004-06-10

  The invention relates to the use of a PDE4 or PDE3/4 inhibitor for the treatment of cachexia.
• Phosphodiesterase Type IV Inhibition. Structure-Activity Relationships of 1,3-Disubstituted Pyrrolidines
  作者：Paul L. Feldman、Marcus F. Brackeen、David J. Cowan、Brian E. Marron、Frank J. Schoenen、Jeffrey A. Stafford、Edward M. Suh、Paul L. Domanico、Dudley Rose

  DOI：10.1021/jm00009a011

  日期：1995.4

  The synthesis of 1,3-disubstituted pyrrolidines 2 and their activities as type IV phosphodiesterase (PDE) inhibitors are described. Various groups were appended to the nitrogen of the pyrrolidine nucleus to enable structure-activity relationships to be assessed. Groups which render the pyrrolidine nitrogen of 2 nonbasic yielded potent PDE-IV inhibitors. Analogs of amides, carbamates, and ureas of 2 were synthesized to determine the effects that substitution on these functional groups had on PDE-IV inhibitor potency. The structural requirements for PDE-IV inhibitor potency differed among the three classes. A representative amide, carbamate, and urea (2c,d,h) were shown to be >50-fold selective for inhibiting PDE-IV versus representative PDEs from families I-III and V. Furthermore, these same three inhibitors demonstrated potent functional activity (IC50 < 1 mu M) by inhibiting tumor necrosis factor-alpha (TNF-alpha) release from lipopolysaccharide (LPS)-activated purified human peripheral blood monocytes and mouse peritoneal macrophages. These compounds were also tested orally in LPS-injected mice and demonstrated dose-dependent inhibition of serum TNF-alpha levels.