1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate | 1167416-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate
• 英文别名: tert-butyl 9-[(Z)-N'-hydroxycarbamimidoyl]-3,5-dihydro-2H-1,4-benzoxazepine-4-carboxylate
• CAS: 1167416-51-4
• 化学式: C₁₅H₂₁N₃O₄
• 分子量: 307.349
• InChiKey: AOPITMDJJDIECW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 在 吡啶 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.5h， 生成 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-9-yl)-1,2,4-oxadiazol-5-yl]benzonitrile trifluoroacetate
  参考文献：
  名称：

  Discovery of a Brain-Penetrant S1P₃-Sparing Direct Agonist of the S1P₁ and S1P₅ Receptors Efficacious at Low Oral Dose

  摘要：

  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).

  DOI：

  10.1021/jm200609t
• 作为产物：
  描述：

  1,1-dimethylethyl 9-cyano-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 生成 1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate
  参考文献：
  名称：

  [EN] OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (SIP)
  [FR] DÉRIVÉS D'OXADIAZOLE ACTIFS SUR LA SPHINGOSINE-1-PHOSPHATE (S1P)

  摘要：

  本申请披露了一种基于噁二唑的化合物，其化学式为（I），对神经酰胺-1-磷脂酸（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；R1为最多两个取代基，可独立选择自卤素、C（1-3）烷氧基、C（1-3）氟烷基、氰基、可选择取代的苯基、C（1-3）氟烷氧基、C（1-6）烷基和C（3-6）环烷基；R2为氢、卤素或C（1-4）烷基；B为以下选项中的7元饱和环之一：（a）（b）（c）；R3为氢或（CH2）1-4MCO2H；R4为氢或C（1-3）烷基，可由氧原子中断。

  公开号：

  WO2009080725A1

文献信息

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

  公开号：WO2009080725A1

  公开（公告）日：2009-07-02

  The present application discloses oxadiazole 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 heteroaryl ring; R1 is up to two substituents independently selected from halogen, C(1-3)aIkoxy, C(1-3)flyoroalkyl, cyano, optionally substituted phenyl. C(1-3)fluoroalkoxy. C(1-6)alkyl and C(3-6)Cyctoalkyl; R2 is hydrogen, halogen or C(1-4)alkyl; B is a 7 membered saturated ring selected from the following: Formulae (a) (b) (c) R3 is hydrogen or (CH2)1-4MCO2H; R4 is hydrogen or C(1-3)alkyl optionally interrupted by oxygen;

  本申请披露了一种基于噁二唑的化合物，其化学式为（I），对神经酰胺-1-磷脂酸（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；R1为最多两个取代基，可独立选择自卤素、C（1-3）烷氧基、C（1-3）氟烷基、氰基、可选择取代的苯基、C（1-3）氟烷氧基、C（1-6）烷基和C（3-6）环烷基；R2为氢、卤素或C（1-4）烷基；B为以下选项中的7元饱和环之一：（a）（b）（c）；R3为氢或（CH2）1-4MCO2H；R4为氢或C（1-3）烷基，可由氧原子中断。
• COMPOUNDS
  申请人：HEER Jag Paul

  公开号：US20100174065A1

  公开（公告）日：2010-07-08

  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二唑衍生物，其制备方法，含有它们的药物组合物以及它们在治疗各种疾病中的用途。
• Oxadiazole derivatives active on sphingosine-1-phosphate (S1P)
  申请人：Glaxo Group Limited

  公开号：US08222245B2

  公开（公告）日：2012-07-17

  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二唑衍生物，其制备过程，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 (SIP)
  申请人：Demont Emmanuel Hubert

  公开号：US20100273771A1

  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中的用途。
• US8222245B2
  申请人：——

  公开号：US8222245B2

  公开（公告）日：2012-07-17