8-甲氧基-3,4-二氢苯并[F][1,4]氧氮杂-5(2H)-酮 | 5755-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 8-甲氧基-3,4-二氢苯并[F][1,4]氧氮杂-5(2H)-酮
• 英文名称: 8-(methyloxy)-3,4-dihydro-1,4-benzoxazepin-5(2H)-one
• 英文别名: 8-methoxy-3,4-dihydro-2H-1,4-benzoxazepin-5-one；8-methoxy-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one；8-Methoxy-2,3-dihydro-4H-<1,4>-benzoxazepin-5-on；8-Methoxy-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one
• CAS: 5755-00-0
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: HPFHVUXTDUJDAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-甲氧基-3,4-二氢苯并[F][1,4]氧氮杂-5(2H)-酮 在 吡啶 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 110.0 ℃ 、101.33 kPa 条件下， 反应 33.5h， 生成 1,1-dimethylethyl 8-cyano-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate
  参考文献：
  名称：

  Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

  摘要：

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

  DOI：

  10.1021/jm5010336
• 作为产物：
  描述：

  4-甲氧基水杨酸甲酯 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 67.0h， 生成 8-甲氧基-3,4-二氢苯并[F][1,4]氧氮杂-5(2H)-酮
  参考文献：
  名称：

  Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

  摘要：

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

  DOI：

  10.1021/jm5010336

文献信息

• Synthesis and evaluation of novel 2,4-diaminopyrimidines bearing bicyclic aminobenzazepines for anaplastic lymphoma kinase (ALK) inhibitor
  作者：Ga Ae Kang、Minji Lee、Dawn Song、Heung Kyoung Lee、Sunjoo Ahn、Chi Hoon Park、Chong Ock Lee、Chang Soo Yun、Heejung Jung、Pilho Kim、Jae Du Ha、Sung Yun Cho、Hyoung Rae Kim、Jong Yeon Hwang

  DOI：10.1016/j.bmcl.2015.07.004

  日期：2015.9

  A series of novel 2,4-diaminopyrimidine compounds bearing bicyclic aminobenzazepine were synthesized and evaluated for their anti-ALK activities. The activities of these compounds were confirmed in both enzyme- and cell-based ALK assays. Amongst compounds synthesized, KRCA-0445 showed very promising results in pharmacokinetic study and in vivo efficacy study with H3122 xenograft mouse model.

  合成了一系列带有双环氨基苯并ze庚因的新型2，4-二氨基嘧啶化合物，并评估了其抗ALK活性。这些化合物的活性均在基于酶和细胞的ALK分析中得到证实。在合成的化合物中，KRCA-0445在H3122异种移植小鼠模型的药代动力学研究和体内功效研究中显示出非常有希望的结果。
• BICYCLIC COMPOUND AND USE THEREOF
  申请人：SK BIOPHARMACEUTICALS CO., LTD.

  公开号：US20210101892A1

  公开（公告）日：2021-04-08

  The present disclosure relates to a compound derivative containing a 6-7 bicyclic ring and use thereof. The compound according to the present invention can be effectively used in the prevention or treatment of diseases caused by PRMT5 by acting as a PRMT5 inhibitor.

  本公开涉及一种含有6-7环状结构的化合物衍生物及其用途。根据本发明的化合物可作为PRMT5抑制剂，能够有效地用于预防或治疗由PRMT5引起的疾病。
• [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。
• The synthesis and proton magnetic resonance spectra of 2,3-dihydro-1,4-benzoxazepin-5(4H)-ones
  作者：G. S. Sidhu、G. Thyagarajan、U. T. Bhalerao

  DOI：10.1039/j39660000969

  日期：——

  4-benzoxazepin-5(4H)-ones carrying substituents in the aromatic ring have been synthesised. The parent compound has also been prepared in considerably better yields than reported by earlier workers. P.m.r. spectra have been used to distinguish between the isomeric 1,4- and 1,5-benzoxazepin-ones.

  合成了在芳族环中带有取代基的八个2，3-二氢-1，4-苯并恶唑啉-5（4 H）-1 。母体化合物的制备也比早期工人报告的产率要好得多。Pmr光谱已用于区分异构体1,4-和1,5-苯并恶嗪-酮。