6-{[(2R)-3-(4-fluorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenecarbaldehyde | 872710-02-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-{[(2R)-3-(4-fluorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenecarbaldehyde
• 英文别名: 6-[(2R)-3-(4-fluorophenyl)-2-methylpropoxy]-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde
• CAS: 872710-02-6
• 化学式: C₂₂H₂₃FO₂
• 分子量: 338.422
• InChiKey: KULYGTXXUXLYFC-OAHLLOKOSA-N

物化性质

• 沸点：
  491.5±45.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-{[(2R)-3-(4-fluorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenecarbaldehyde 在 水 、 三乙酰氧基硼氢化钠 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 1-[(6-{[(2R)-3-(4-fluorophenyl)-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 、 potassium carbonate 、 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 6-{[(2R)-3-(4-fluorophenyl)-2-methylpropyl]oxy}-1-methyl-3,4-dihydro-2-naphthalenecarbaldehyde
  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 Having S1P Receptor Binding Potency and Use Thereof
  申请人：Habashita Hiromu

  公开号：US20080207584A1

  公开（公告）日：2008-08-28

  Provided are: a compound represented by formula (I): (wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocyclic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, in which when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt thereof; an N-oxide form thereof; a solvate thereof, a prodrug thereof; and a medicament which includes those. The compound represented by formula (I) is capable of binding S1P receptors (in particular, EDG-1 and/or EDG-6), and useful for preventing and/or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.

  提供的是一个由式(I)表示的化合物：其中，环A和环D分别表示可以具有取代基的环状基团；E和G分别表示具有1至8个原子的主链上的键或间隔物；L表示氢原子或取代基；X表示可以具有取代基的氨基或含有至少一个氮原子且可以具有取代基的杂环基团；n表示0至3，在其中当n为2或更多时，多个环A可以相同或不同。还提供了该化合物的盐、N-氧化物形式、溶剂化物、前药和包括其的药物。该化合物能够结合S1P受体（特别是EDG-1和/或EDG-6），并用于预防和/或治疗移植排斥、自身免疫性疾病、过敏性疾病等。
• COMPOUND HAVING S1P RECEPTOR BINDING POTENCY AND USE THEREOF
  申请人：HABASHITA Hiromu

  公开号：US20120064060A1

  公开（公告）日：2012-03-15

  Provided are: a compound represented by formula (I): (wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocylic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, and when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt, an N-oxide form, a solvate, or a prodrug thereof; and a medicament which includes those. The compound of formula (I) is capable of binding S1P receptors (in particular, EDG-1 and/or EDG-6), and useful for preventing and/or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.

  提供了一个由式(I)表示的化合物：（其中，环A和环D分别表示可能具有取代基的环状基团；E和G分别表示具有1-8个原子的主链中的键或间隔物；L表示氢原子或取代基；X表示氨基，可能具有取代基，或者含有至少一个氮原子且可能具有取代基的杂环基团；n表示0-3，当n为2或更多时，多个环A可以相同或不同）。还提供了该化合物的盐、N-氧化物形式、溶剂合物或前药；以及包括这些的药物。式(I)化合物能够结合S1P受体（特别是EDG-1和/或EDG-6），用于预防和/或治疗移植排斥、自身免疫性疾病、过敏性疾病等。
• US8039674B2
  申请人：——

  公开号：US8039674B2

  公开（公告）日：2011-10-18
• US8653305B2
  申请人：——

  公开号：US8653305B2

  公开（公告）日：2014-02-18
• 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.