{1-[(2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]-1H-pyrrol-3-yl}acetic acid | 856691-83-3

• 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: {1-[(2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]-1H-pyrrol-3-yl}acetic acid
• 英文别名: 2-[1-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]pyrrol-3-yl]acetic acid
• CAS: 856691-83-3
• 化学式: C₃₄H₄₇NO₅Si
• 分子量: 577.836
• InChiKey: NAXVPJGARXUBKQ-RYCFQHDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.63
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {1-[(2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]-1H-pyrrol-3-yl}acetic acid 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 {1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrol-3-yl}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：

  苯(甲)醛,3,5-二甲氧基-4-甲基- 在 2,6-二甲基吡啶 、 锂硼氢 、 三甲基氯硅烷 、 sodium hydride 、 三乙胺 、 sodium hydroxide 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 乙二醇 、 乙酸乙酯 、 正丁醇 为溶剂， 反应 9.0h， 生成 {1-[(2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]-1H-pyrrol-3-yl}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

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