(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenyl-1-pentanol | 856687-71-3

• 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: (2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenyl-1-pentanol
• 英文别名: (2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentan-1-ol；(2S)-2-[(S)-[tert-butyl(dimethyl)silyl]oxy-(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentan-1-ol
• CAS: 856687-71-3
• 化学式: C₂₇H₄₂O₄Si
• 分子量: 458.714
• InChiKey: PPXVXTRQJDQFSK-NVQXNPDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.71
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenyl-1-pentanol 在 lithium aluminium tetrahydride 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 sodium iodide 、 lithium chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 6.83h， 生成 (1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenylpentyl}-1H-pyrazol-4-yl)acetonitrile
  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 、 三乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 5.08h， 生成 (2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl){[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl]-5-phenyl-1-pentanol
  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