1-[[6-[3-(3-Fluorophenyl)propoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid | 847736-94-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-[[6-[3-(3-Fluorophenyl)propoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid
• CAS: 847736-94-1
• 化学式: C₂₅H₂₈FNO₃
• 分子量: 409.501
• InChiKey: YJVGDVPBEKGCSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[[6-[3-(3-Fluorophenyl)propoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 1-({6-[3-(3-fluorophenyl)propoxy]-1-methyl-3,4-dihydro-2-naphthalenyl}methyl)-3-azetidinecarboxylic acid hydrochloride
  参考文献：
  名称：

  Structure–activity relationship studies of S1P agonists with a dihydronaphthalene scaffold

  摘要：

  Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.048
• 作为产物：
  描述：

  3-(3-氟苯基)丙酸 在 硼烷四氢呋喃络合物 、 偶氮二甲酰胺 、 三苯基膦 、 sodium hydroxide 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 1-[[6-[3-(3-Fluorophenyl)propoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid
  参考文献：
  名称：

  Structure–activity relationship studies of S1P agonists with a dihydronaphthalene scaffold

  摘要：

  Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.048

文献信息

• COMPOUND CAPABLE OF BINDING S1P RECEPTOR AND PHARMACEUTICAL USE THEREOF
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1661881B1

  公开（公告）日：2014-12-17
• Structure–activity relationship studies of S1P agonists with a dihydronaphthalene scaffold
  作者：Haruto Kurata、Kensuke Kusumi、Kazuhiro Otsuki、Ryo Suzuki、Masakuni Kurono、Natsuko Tokuda、Yuka Takada、Hiroki Shioya、Hirotaka Mizuno、Takaki Komiya、Takeji Ono、Hiroshi Hagiya、Masashi Minami、Shinji Nakade、Hiromu Habashita

  DOI：10.1016/j.bmcl.2011.11.048

  日期：2012.1

  Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. (C) 2011 Elsevier Ltd. All rights reserved.