1-({6-[3-(3-fluorophenyl)propoxy]-1-methyl-3,4-dihydro-2-naphthalenyl}methyl)-3-azetidinecarboxylic acid hydrochloride | 847585-23-3

• 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-dihydro-2-naphthalenyl}methyl)-3-azetidinecarboxylic acid hydrochloride
• 英文别名: 1-[[6-[3-(3-Fluorophenyl)propoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylic acid;hydrochloride
• CAS: 847585-23-3
• 化学式: C₂₅H₂₈FNO₃*ClH
• 分子量: 445.962
• InChiKey: IUWOMPIRUPFCCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.0
• 重原子数：
  31
• 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：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(3-氟苯基)丙酸 在 盐酸 、 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 、 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

文献信息

• Compound capable of binding s1p receptor and pharmaceutical use thereof
  申请人：Nakade Shinji

  公开号：US20070167425A1

  公开（公告）日：2007-07-19

  A compound having an ability to bind to an S 1 P receptor (particularly EDG-6, preferably EDG-1 and EDG-6), for example, the compound represented by formula (I) of the present invention, a salt thereof, a solvate thereof or a prodrug thereof is useful for prevention and/or treatment of rejection of transplantation, graft-versus-host disease, autoimmune disease, allergic disease and the like. wherein ring A is a cyclic group; ring B is a cyclic group which may have substituent(s); X is a spacer having 1 to 8 atoms in its main chain, etc.; Y is a spacer having 1 to 10 atoms in its main chain, etc.; n is 0 or 1, wherein when n is 0, m is 1 and R 1 is a hydrogen atom or a substituent, and wherein when n is 1, m is 0 or an integer of 1 to 7 and R 1 is a substituent, and wherein m is 2 or more, R 1 s are the same or different.

  一种具有结合S1P受体的能力的化合物（特别是EDG-6，最好是EDG-1和EDG-6），例如本发明的式（I）所表示的化合物，其盐，溶剂合物或前药，对于预防和/或治疗移植排斥，移植物抗宿主病，自身免疫性疾病，过敏性疾病等是有用的。其中，环A是一个环状基团；环B是一个可能具有取代基的环状基团；X是具有1至8个原子的主链的间隔物等；Y是具有1至10个原子的主链的间隔物等；n为0或1，其中当n为0时，m为1且R1是氢原子或取代基，当n为1时，m为0或1至7的整数且R1是取代基，当m为2或更多时，R1相同或不同。
• 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
• Compound capable of binding S1P receptor and pharmaceutical use thereof
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP2883865B1

  公开（公告）日：2019-09-25
• US7825109B2
  申请人：——

  公开号：US7825109B2

  公开（公告）日：2010-11-02
• US8791159B2
  申请人：——

  公开号：US8791159B2

  公开（公告）日：2014-07-29