tert-butyl 6-(5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate | 1165923-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 6-(5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate
• 英文别名: 1,1-dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate；tert-butyl 6-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]-5-methyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 1165923-99-8
• 化学式: C₂₆H₃₀ClN₃O₄
• 分子量: 483.995
• InChiKey: ACBTVBPBWAVOQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-(5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 4.5h， 生成 methyl [6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinyl]acetate
  参考文献：
  名称：

  [EN] S1P1 AGONISTS COMPRISING A BICYCLIC N-CONTAINING RING
  [FR] AGONISTES DE S1P1 COMPRENANT UN CYCLE AZOTÉ BICYCLIQUE

  摘要：

  本发明涉及具有S1P1激动剂活性的式(I)新化合物，其制备方法，包含它们的药物组合物及其用于治疗各种疾病的应用。

  公开号：

  WO2010146105A1
• 作为产物：
  描述：

  6-氰基-5-甲基-3,4-二氢异喹啉-2(1h)-羧酸叔丁酯 在 吡啶 、 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 30.5h， 生成 tert-butyl 6-(5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate
  参考文献：
  名称：

  Discovery of a Selective S1P₁ Receptor Agonist Efficacious at Low Oral Dose and Devoid of Effects on Heart Rate

  摘要：

  Gilenya (fingolimod, FTY720) was recently approved by the U.S. FDA for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). It is a potent agonist of four of the five sphingosine 1-phosphate (SIP) G-protein-coupled receptors (S1P(1) and S1P(3-5)). It has been postulated that fingolimod's efficacy is due to S1P(1) agonism, while its cardiovascular side effects (transient bradycardia and hypertension) are due to S1P(3) agonism. We have discovered a series of selective S1P(1), agonists, which includes 3-[6- (5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl- 3,4-dihydro-2(1H)-isoquinolinyl]propanoate, 20, a potent, S1P(3)-sparing, orally active S1P(1) agonist. Compound 20 is as efficacious as fingolimod in a collagen-induced arthritis model and shows excellent pharmacokinetic properties preclinically. Importantly, the selectivity of 20 against S1P(3) is responsible for an absence of cardiovascular signal in telemetered rats, even at high dose levels.

  DOI：

  10.1021/ml2000214

文献信息

• [EN] OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (S1P)<br/>[FR] DÉRIVÉS D'OXADIAZOLE ACTIFS SUR LA SPHINGOSINE-1-PHOSPHATE (S1P)
  申请人：GLAXO GROUP LTD

  公开号：WO2009080724A1

  公开（公告）日：2009-07-02

  The present application discloses oxadiazote based compounds of Formula (I) active on sphingosine-1-phosphate (S1P) in particular useful to treat lupus erythematosus. A is phenyl or a 5 or 6-membered heleroaryl ring; B is selected from one of the following; Formulae: (a) (b) (c)

  本申请公开了一种基于噁二唑酮的化合物，其化学式为（I），对神经酰胺-1-磷酸酯（S1P）具有活性，特别适用于治疗红斑狼疮。其中，A为苯基或5或6元杂环芳基环；B从以下化合物中选择一个：化学式：（a）（b）（c）。
• Oxadiazole derivatives active on sphingosine-1-phosphate (S1P)
  申请人：Glaxo Group Limited

  公开号：US08278324B2

  公开（公告）日：2012-10-02

  The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

  本发明涉及具有药理活性的新型噁唑二嗪衍生物、其制备方法、含有它们的制药组合物以及它们在治疗各种疾病中的应用。
• OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (S1P)
  申请人：Heer Jag Paul

  公开号：US20100152235A1

  公开（公告）日：2010-06-17

  The present invention relates to a novel oxadiazole derivative having pharmacological activity, processes for its preparation, pharmaceutical compositions containing it and its use in the treatment of various disorders.

  本发明涉及一种具有药理活性的新型噁二唑衍生物，其制备过程、含有该衍生物的制药组合物以及其在治疗各种疾病中的应用。
• S1P1 AGONISTS COMPRISING A BICYCLIC N-CONTAINING RING
  申请人：Bailey James Matthew

  公开号：US20120101083A1

  公开（公告）日：2012-04-26

  The present invention relates to novel compounds of formula (I) having S1P1 agonist activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

  本发明涉及具有S1P1激动剂活性的公式（I）的新化合物，其制备过程，含有它们的药物组合物以及它们在治疗各种疾病中的应用。
• OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (S1p)
  申请人：Heer Jag Paul

  公开号：US20100273827A1

  公开（公告）日：2010-10-28

  The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

  本发明涉及具有药理活性的新型噁唑烷衍生物，其制备方法，含有它们的制药组合物以及它们在治疗各种疾病方面的应用。