5-(3-chloro-phenylcarbamoyl)pentanoic acid pentyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(3-chloro-phenylcarbamoyl)pentanoic acid pentyl ester
• 英文别名: 5-(3-Chloro-phenylcarbamoyl)-pentanoic acid pentyl ester；pentyl 6-(3-chloroanilino)-6-oxohexanoate
• 化学式: C₁₇H₂₄ClNO₃
• 分子量: 325.835
• InChiKey: IQHCNEGTPWVMDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氯苯胺 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 生成 5-(3-chloro-phenylcarbamoyl)pentanoic acid pentyl ester
  参考文献：
  名称：

  Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility

  摘要：

  Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group on the right side of carbonyl group of the amide pharmacophore substituted with an adamantyl group (such as compound 14) and a methylene carbon present between the adamantyl and amide groups were essential to produce potent inhibition of sEH. The resulting amide inhibitors have 10-30-fold better solubility and lower melting point than the corresponding urea compounds. These findings will facilitate synthesis of sEH inhibitors that are easier to formulate and more bioavailable.

  DOI：

  10.1021/jm0500929

文献信息

• Inhibitors for the soluble epoxide hydrolase
  申请人：Hammock D. Bruce

  公开号：US20060270609A1

  公开（公告）日：2006-11-30

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。
• Inhibitors for the Soluble Epoxide Hydrolase
  申请人：HAMMOCK BRUCE D.

  公开号：US20110021448A1

  公开（公告）日：2011-01-27

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。
• [EN] IMPROVED INHIBITORS FOR THE SOLUBLE EPOXIDE HYDROLASE<br/>[FR] INHIBITEURS AMELIORES DE L'EPOXYDE HYDROLASE SOLUBLE
  申请人：UNIV CALIFORNIA

  公开号：WO2006045119A3

  公开（公告）日：2007-02-08
• US7662910B2
  申请人：——

  公开号：US7662910B2

  公开（公告）日：2010-02-16
• US8476043B2
  申请人：——

  公开号：US8476043B2

  公开（公告）日：2013-07-02