1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentyl}-1H-pyrazole-4-carbaldehyde | 856688-70-5

• 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)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentyl}-1H-pyrazole-4-carbaldehyde
• 英文别名: 1-{(2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl}-1H-pyrazole-4-carbaldehyde；1-[(2S)-2-[(S)-[tert-butyl(dimethyl)silyl]oxy-(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl]pyrazole-4-carbaldehyde
• CAS: 856688-70-5
• 化学式: C₃₁H₄₄N₂O₄Si
• 分子量: 536.787
• InChiKey: KOMMQJRXAGNDEK-YZNIXAGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.42
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentyl}-1H-pyrazole-4-carbaldehyde 在 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 13.67h， 生成 3-(1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentyl}-1H-pyrazol-4-yl)propanoic 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 、 lithium aluminium tetrahydride 、 锂硼氢 、 三甲基氯硅烷 、 三氧化硫吡啶 、 potassium carbonate 、 三乙胺 、 sodium iodide 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 11.58h， 生成 1-{(2S)-2-[(S)-(3,5-dimethoxy-4-methylphenyl)(hydroxy)methyl]-5-phenylpentyl}-1H-pyrazole-4-carbaldehyde
  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
• Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia
  作者：Masahiko Terakado、Hidehiro Suzuki、Kazuya Hashimura、Motoyuki Tanaka、Hideyuki Ueda、Keisuke Hirai、Masaki Asada、Masahiro Ikura、Naoki Matsunaga、Hiroshi Saga、Koji Shinozaki、Naoko Karakawa、Yuka Takada、Masashi Minami、Hiromu Egashira、Yoshihiro Sugiura、Masanori Yamada、Shinji Nakade、Yoshikazu Takaoka

  DOI：10.1021/acsmedchemlett.7b00383

  日期：2017.12.14

  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.