1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrole-3-carbaldehyde | 856689-47-9

• 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)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrole-3-carbaldehyde
• 英文别名: 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-pyrrole-3-carbaldehyde；1-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)propyl]pyrrole-3-carbaldehyde
• CAS: 856689-47-9
• 化学式: C₃₃H₄₅NO₄Si
• 分子量: 547.81
• InChiKey: PQGHFGFYUSIAJC-BHDXBOSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.81
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrole-3-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 、 乙醇 、 mineral oil 为溶剂， 反应 10.5h， 生成 3-{1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrol-3-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 、 锂硼氢 、 三甲基氯硅烷 、 caesium carbonate 、 三乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-[(2S,3S)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-(3,5-dimethoxy-4-methylphenyl)-3-hydroxypropyl]-1H-pyrrole-3-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.