2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]-3-pyridinecarbonitrile trifluoroacetate | 1258855-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]-3-pyridinecarbonitrile trifluoroacetate
• 英文别名: 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]-3-pyridinecarbonitrile mono-trifluoroacetate；2-propan-2-yloxy-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]pyridine-3-carbonitrile;2,2,2-trifluoroacetic acid
• CAS: 1258855-75-2
• 化学式: C₂HF₃O₂*C₂₁H₂₁N₅O₂
• 分子量: 489.454
• InChiKey: PRKKJTBTFVRVBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]-3-pyridinecarbonitrile trifluoroacetate 在 盐酸 、 水 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 86.25h， 生成 5-(3-{3-[2-hydroxy-1-(hydroxymethyl)ethyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl}-1,2,4-oxadiazol-5-yl)-2-[(1-methylethyl)oxy]-3-pyridinecarbonitrile
  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：

  7-氰基-1,2,4,5-四氢-3H-苯并[D]氮杂-3-羧酸叔丁酯 在 吡啶 、 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.33h， 生成 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,2,4-oxadiazol-5-yl]-3-pyridinecarbonitrile trifluoroacetate
  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

文献信息

• 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。
• Discovery of a Brain-Penetrant S1P₃-Sparing Direct Agonist of the S1P₁ and S1P₅ Receptors Efficacious at Low Oral Dose
  作者：Emmanuel H. Demont、Sandra Arpino、Rino A. Bit、Colin A. Campbell、Nigel Deeks、Sapna Desai、Simon J. Dowell、Pam Gaskin、James R. J. Gray、Lee A. Harrison、Andrea Haynes、Tom D. Heightman、Duncan S. Holmes、Philip G. Humphreys、Umesh Kumar、Mary A. Morse、Greg J. Osborne、Terry Panchal、Karen L. Philpott、Simon Taylor、Robert Watson、Robert Willis、Jason Witherington

  DOI：10.1021/jm200609t

  日期：2011.10.13

  2-Amino-2-(4-octylphenethyl)propane-1,3-diol 1 (fingolimod, FTY720) has been recently marketed in the United States for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). Its efficacy has been primarily linked to the agonism on T cells of S1P(1), one of the five sphingosine 1-phosphate (S1P) G-protein-coupled receptors, while its cardiovascular side effects have been associated with activity at S1P(3). Emerging data suggest that the ability of this molecule to cross the blood-brain barrier and to interact with both S1P(1) and S1P(5) in the central nervous system (CNS) may contribute to its efficacy in treating patients with RAMS. We have recently disclosed the structure of an advanced, first generation S1P(3)-sparing S1P(1) agonist, a zwitterion with limited CNS exposure. In this Article, we highlight our strategy toward the identification of CNS-penetrant S1P(3)-sparing S1P(1) and S1P5 agonists resulting in the discovery of 5-(3-2-[2-hydroxy-1- (hydroxymethyl)ethyl]-5-methyl-1,2,3,4-tetrahydro-6-isoquinolinyl}-1,2,4-oxadiazol-5-yl)-2-[(1-methylethyl)oxy]benzonitrile 15. Its exceptional in vivo potency and good pharmacokinetic properties translate into a very low predicted therapeutic dose in human (< 1 mg p.o. once daily).
• [EN] S1P1 AGONISTS COMPRISING A BICYCLIC N-CONTAINING RING<br/>[FR] AGONISTES DE S1P1 COMPRENANT UN CYCLE AZOTÉ BICYCLIQUE
  申请人：GLAXO GROUP LTD

  公开号：WO2010146105A1

  公开（公告）日：2010-12-23

  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。