methyl cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane- 1-carboxylate] | 153259-62-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane- 1-carboxylate]
• 英文别名: methyl cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylate]；Methyl cis-[4-Cyano-4-(3cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylate]
• CAS: 153259-62-2
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: WUSGLEFPBNJHCW-GGYDESQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  68.55
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane- 1-carboxylate] 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 cilomilast
  参考文献：
  名称：

  Repurposing human PDE4 inhibitors for neglected tropical diseases: Design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors

  摘要：

  A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation.

  DOI：

  10.1016/j.bmcl.2014.07.063
• 作为产物：
  描述：

  在 正丁基锂 、 高氯酸 、 sodium chloride 、 mercury dichloride 作用下， 以 二甲基亚砜 为溶剂， 反应 49.33h， 生成 methyl cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane- 1-carboxylate]
  参考文献：
  名称：

  1,4-Cyclohexanecarboxylates:  Potent and Selective Inhibitors of Phosophodiesterase 4 for the Treatment of Asthma

  摘要：

  Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [H-3]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1 -carboxylic acid (1, SB 207499, Ariflo(TM)), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram.

  DOI：

  10.1021/jm970090r

文献信息

• Compounds useful for treating allergic and inflammatory diseases
  申请人：SmithKline Beecham Corporation

  公开号：US05552438A1

  公开（公告）日：1996-09-03

  Novel compounds of Formula (I) ##STR1## where X.sub.4 is a substituted cyclohexane or cyclohexane group and the other radicals are defined herein. These compounds inhibit the production of Tumor Necrosis Factor and are useful in the treatment of disease states mediated or exacerbated by TNF production. The compounds of the present invention are also useful in the mediation or inhibition of enzymatic or catalytic activity of phosphodiesterase IV and are therefore useful in the treatment of disease states in need of mediation or inhibition thereof.

  化合物的新颖结构如下式（I）##STR1##其中X.sub.4是取代的环己烷或环己烷基团，其他基团在此有定义。这些化合物抑制肿瘤坏死因子的产生，并可用于治疗由TNF产生介导或加重的疾病状态。本发明的化合物还可用于介导或抑制磷酸二酯酶IV的酶活性，因此可用于治疗需要介入或抑制的疾病状态。
• Compounds usefulfor treating allergic and inflammatory diseases
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1420011A1

  公开（公告）日：2004-05-19

  Certain compounds of formulae (I) and (IA) are disclosed for use in the treatment and prophylaxis of arthritic conditions.

  式 (I) 和 (IA) 的某些化合物 公开了用于治疗和预防关节炎的化合物。
• COMPOUNDS USEFUL FOR TREATING ALLERGIC AND INFLAMMATORY DISEASES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0633776B1

  公开（公告）日：2001-05-09
• METHOD FOR TREATING MULTIPLE SCLEROSIS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1043994A1

  公开（公告）日：2000-10-18
• EP1043994A4
  申请人：——

  公开号：EP1043994A4

  公开（公告）日：2002-09-11