methyl {4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl}acetate | 1224301-15-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: methyl {4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl}acetate
• 英文别名: Methyl 2-[4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl]acetate
• CAS: 1224301-15-8
• 化学式: C₃₀H₃₄O₅
• 分子量: 474.597
• InChiKey: SHWJTCQWGAXYOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl {4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl}acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以43%的产率得到2-[4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl]acetic acid
  参考文献：
  名称：

  Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  Scaffold hopping from the amide group of lead compound ONO 7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA(1)) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPAI receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [H-3]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.

  DOI：

  10.1021/acsmedchemlett.7b00383
• 作为产物：
  描述：

  1-氯-3-苯基丙烷 在 五甲基二乙烯三胺 、 magnesium 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.83h， 生成 methyl {4-[2-(3,5-dimethoxy-4-methylbenzoyl)-5-phenylpentyl]phenyl}acetate
  参考文献：
  名称：

  Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  Scaffold hopping from the amide group of lead compound ONO 7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA(1)) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPAI receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [H-3]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.

  DOI：

  10.1021/acsmedchemlett.7b00383

文献信息

• COMPOUNDS HAVING LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISM AND USES THEREOF
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1695955B1

  公开（公告）日：2011-10-12