methyl 1-[(6-{[(2S)-3-(4-chlorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenyl)methyl]-3-azetidinecarboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 1-[(6-{[(2S)-3-(4-chlorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenyl)methyl]-3-azetidinecarboxylate
• 英文别名: methyl 1-[[6-[(2S)-3-(4-chlorophenyl)-2-methylpropoxy]-1-methyl-3,4-dihydronaphthalen-2-yl]methyl]azetidine-3-carboxylate
• 化学式: C₂₇H₃₂ClNO₃
• 分子量: 454.009
• InChiKey: ATKLFPCBNXLMSJ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-[(6-{[(2S)-3-(4-chlorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenyl)methyl]-3-azetidinecarboxylate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1-[(6-{[(2S)-3-(4-chlorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2 - naphthalenyl)methyl]-3-azetidinecarboxylic 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
• 作为产物：
  描述：

  6-羟基-1-四氢萘酮 在 盐酸 、 茴香硫醚 、 偶氮二甲酰胺 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醚 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 生成 methyl 1-[(6-{[(2S)-3-(4-chlorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenyl)methyl]-3-azetidinecarboxylate
  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

• AMINOCARBOXYLIC ACID DERIVATIVE AND MEDICINAL USE THEREOF
  申请人：Habashita Hiromu

  公开号：US20090275554A1

  公开（公告）日：2009-11-05

  The present invention relates to a compound represented by the formula (I), a salt thereof, an N-oxide form thereof, a solvate thereof, or a prodrug thereof, and a medicament containing the same. The compound represented by the formula (I) has an ability to bind to an S1P receptor (particularly, EDG-1, EDG-6, and/or EDG-8) and is useful for preventing and/or treating for rejection to transplantation, graft-versus-host disease, autoimmune diseases, allergic diseases, neurodegenerating diseases, and the like. wherein all symbols are described in the specification.

  本发明涉及一种由公式（I）表示的化合物，其盐，其N-氧化物形式，其溶剂化物或其前药，以及含有该化合物的药物。公式（I）表示的化合物具有结合S1P受体（特别是EDG-1，EDG-6和/或EDG-8）的能力，可用于预防和/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，神经退行性疾病等。其中所有符号在说明书中描述。
• Azetidinecarboxylic acid derivative and medicinal use thereof
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP2371811A2

  公开（公告）日：2011-10-05

  A compound represented by the formula (IC-2), a salt thereof, an N-oxide form thereof, a solvate thereof, a prodrug thereof, or a number of specific compounds and pharmaceutical compositions comprising these compounds. The compound has the ability to combine with an SIP receptor (especially EDG-1, EDG-6 and/or EDG-8). It is useful for the prevention and/or treatment of rejection reactions to transplantation, graft versus host diseases, autoimmune diseases, allergic diseases, neurodegenerative diseases etc.

  由式（IC-2）代表的化合物、其盐、其 N-氧化物形式、其溶液剂、其原药或一些特定化合物以及包含这些化合物的药物组合物。该化合物具有与 SIP 受体（尤其是 EDG-1、EDG-6 和/或 EDG-8）结合的能力。它可用于预防和/或治疗移植排斥反应、移植物抗宿主疾病、自身免疫性疾病、过敏性疾病、神经退行性疾病等。
• Aminocarboxylic acid derivative and medical use thereof
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP2592066B1

  公开（公告）日：2014-12-03
• US7906549B2
  申请人：——

  公开号：US7906549B2

  公开（公告）日：2011-03-15
• US8575134B2
  申请人：——

  公开号：US8575134B2

  公开（公告）日：2013-11-05