6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde | 847585-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde
• CAS: 847585-92-6
• 化学式: C₁₂H₁₂O₂
• 分子量: 188.226
• InChiKey: RMSLYHOBSSTINB-UHFFFAOYSA-N

物化性质

• 沸点：
  362.0±42.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde 在 盐酸 、 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-{[1-methyl-6-(1-methyl-3-phenylpropoxy)-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：

  6-羟基-1-四氢萘酮 在 茴香硫醚 、 potassium carbonate 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醚 、 丙酮 为溶剂， 反应 10.33h， 生成 6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde
  参考文献：
  名称：

  DIHYDRONAPHTHALENE DERIVATIVES USEFUL IN THE TREATMENT OF S1P5-MEDIATED DISEASES

  摘要：

  公开号：

  EP3228615B1
• 作为试剂：
  描述：

  1-(bromomethyl)-2-methoxy-4-propylbenzene 、 6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde 在 6-hydroxy-1-methyl-3,4-dihydronaphthalene-2-carbaldehyde 作用下， 以88的产率得到6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydro-2-naphthalenecarbaldehyde
  参考文献：
  名称：

  J. Med. Chem. 2017, 60, 9508-9530

  摘要：

  DOI：

文献信息

• Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P₁ and S1P₅ Selective Agonist for the Treatment of Autoimmune Diseases
  作者：Haruto Kurata、Kensuke Kusumi、Kazuhiro Otsuki、Ryo Suzuki、Masakuni Kurono、Takaki Komiya、Hiroshi Hagiya、Hirotaka Mizuno、Hiroki Shioya、Takeji Ono、Yuka Takada、Tatsuo Maeda、Norikazu Matsunaga、Tetsu Kondo、Sachiko Tominaga、Ken-ici Nunoya、Hidekazu Kiyoshi、Masaharu Komeno、Shinji Nakade、Hiromu Habashita

  DOI：10.1021/acs.jmedchem.7b00785

  日期：2017.12.14

  lic acid 13n (ceralifimod, ONO-4641), a sphingosine-1-phosphate (S1P) receptor agonist selective for S1P1 and S1P5, is described. While it has been revealed that the modulation of the S1P1 receptor is an effective way to treat autoimmune diseases such as relapsing–remitting multiple sclerosis (RRMS), it was also reported that activation of the S1P3 receptor is implicated in some undesirable effects

  1-（6-[（2-甲氧基-4-丙基苄基）氧基] -1-甲基-3,4-二氢萘-2-基}甲基）氮杂环丁烷-3-羧酸13n（ceralifimod，ONO- （4641），描述了对S1P 1和S1P 5具有选择性的鞘氨醇-1-磷酸（S1P）受体激动剂。尽管已经发现调节S1P 1受体是治疗自身免疫性疾病（例如复发-缓解型多发性硬化症（RRMS））的有效方法，但也有报道称S1P 3受体的激活与某些不良作用有关。我们对命中化合物6进行了结构-活性关系（SAR）研究在亲水性头部区域具有氨基酸部分。在通过诱导构象约束力鉴定具有二氢萘中心核的先导化合物之后，亲脂性尾部区域的优化导致发现13n作为临床候选物，其对S1P 1的选择性比S1P 3高> 30 000倍，并且在小鼠外周淋巴细胞降低（PLL）测试（口服给药24小时后，ED 50 = 0.029 mg / kg）。
• [EN] SPHINGOSINE-1-PHOSPHATE RECEPTOR AGONISTS, METHODS OF PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE AGENT<br/>[FR] AGONISTES DES RÉCEPTEURS DE LA SPHINGOSINE-1-PHOSPHATE, LEURS PROCÉDÉS DE PRÉPARATION, ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT EN TANT QUE PRINCIPE ACTIF
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2014129796A1

  公开（公告）日：2014-08-28

  The present invention relates to novel compounds of Formula 1 as sphingosine-1-phosphate receptor agonists which can be effectively used for the treatment of autoimmune diseases, a method for preparing the same, and a pharmaceutical composition comprising the same as an active component. The compounds according to the present invention are effective on extensive autoimmune diseases and chronic inflammatory diseases including relapsing-remitting multiple sclerosis, and can also be used for treating or preventing immunoregulation disorders.

  本发明涉及一种新的化合物，其化学式为Formula 1，作为鞘氨醇-1-磷酸受体激动剂，可有效用于治疗自身免疫性疾病，以及一种制备该化合物的方法和包含该化合物作为活性成分的药物组合物。根据本发明的化合物对广泛的自身免疫性疾病和慢性炎症性疾病，包括复发-缓解型多发性硬化症等具有有效作用，并且还可用于治疗或预防免疫调节紊乱。
• 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 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 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。