8-benzyloxycarbonyl-3-bromo-1-oxa-2,8-diazaspiro<4.5>dec-2-ene | 138163-13-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 8-benzyloxycarbonyl-3-bromo-1-oxa-2,8-diazaspiro<4.5>dec-2-ene
• 英文别名: Benzyl 3-bromo-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate
• CAS: 138163-13-0
• 化学式: C₁₅H₁₇BrN₂O₃
• 分子量: 353.216
• InChiKey: KQHHISWQKXRFPW-UHFFFAOYSA-N

物化性质

• 沸点：
  454.2±55.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-benzyloxycarbonyl-3-bromo-1-oxa-2,8-diazaspiro<4.5>dec-2-ene 在 palladium on activated charcoal 正丁基锂 、 氢气 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 3.33h， 生成 3-hydroxy-1-oxa-2,8-diazaspiro<4.5>dec-2-ene
  参考文献：
  名称：

  Analogues of the low-efficacy partial GABAA agonist 4-PIOL. Syntheses and in vitro pharmacological studies

  摘要：

  4-PIOL (3-hydroxy-5-(4-piperidyl)isoxazole) is a low-efficacy GABA(A) agonist showing a dominating GABA(A) antagonist profile. Three dihydro analogues of 4-PIOL were synthesized, including (RS)-3-hydroxy-5-(4-piperidyl)-2-isoxazoline (1). The synthesis of 1 was based on a regioselective 1,3-dipolar cyclo-addition reaction between 1-benzyloxycarbonyl-4-vinylpiperidine (7) and bromonitrile oxide, prepared in situ from dibromoformoxime. Furthermore, the spiro analogues of 1 3-hydroxy-1-oxa-2,8-diazaspiro[4.5]dec-2-ene (2) and (RS)-3-hydroxy-1-oxa-2,7-diazaspiro[4.5]dec-2-ene (3) were were synthesized regiospecifically via cycloaddition of bromonitrile oxide to the N-benzyloxycarbonyl-protected forms of 4-methylenepiperidine (11) and 3-methylenepiperidine (15), respectively. In contrast to 4-PIOL, none of the new compounds 1-3 showed detectable effects on the binding of H-3-GABA(A) or the subunit-selective GABA(A) agonist, H-3-THIP, to GABA(A) receptor sites, and they did not significantly affect the muscimol-stimulated binding of H-3-diazepam to the benzodiazepine site of the GABA(A) receptor complex.

  DOI：

  10.1016/0223-5234(91)90198-v
• 作为产物：
  描述：

  1,1-二溴甲醛肟 、 1-Cbz-4-亚甲基哌啶 在 sodium carbonate 作用下， 以 乙酸乙酯 为溶剂， 反应 36.0h， 以74%的产率得到8-benzyloxycarbonyl-3-bromo-1-oxa-2,8-diazaspiro<4.5>dec-2-ene
  参考文献：
  名称：

  Analogues of the low-efficacy partial GABAA agonist 4-PIOL. Syntheses and in vitro pharmacological studies

  摘要：

  4-PIOL (3-hydroxy-5-(4-piperidyl)isoxazole) is a low-efficacy GABA(A) agonist showing a dominating GABA(A) antagonist profile. Three dihydro analogues of 4-PIOL were synthesized, including (RS)-3-hydroxy-5-(4-piperidyl)-2-isoxazoline (1). The synthesis of 1 was based on a regioselective 1,3-dipolar cyclo-addition reaction between 1-benzyloxycarbonyl-4-vinylpiperidine (7) and bromonitrile oxide, prepared in situ from dibromoformoxime. Furthermore, the spiro analogues of 1 3-hydroxy-1-oxa-2,8-diazaspiro[4.5]dec-2-ene (2) and (RS)-3-hydroxy-1-oxa-2,7-diazaspiro[4.5]dec-2-ene (3) were were synthesized regiospecifically via cycloaddition of bromonitrile oxide to the N-benzyloxycarbonyl-protected forms of 4-methylenepiperidine (11) and 3-methylenepiperidine (15), respectively. In contrast to 4-PIOL, none of the new compounds 1-3 showed detectable effects on the binding of H-3-GABA(A) or the subunit-selective GABA(A) agonist, H-3-THIP, to GABA(A) receptor sites, and they did not significantly affect the muscimol-stimulated binding of H-3-diazepam to the benzodiazepine site of the GABA(A) receptor complex.

  DOI：

  10.1016/0223-5234(91)90198-v

文献信息

• [EN] ISOXAZOLINES AS INHIBITORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] ISOXAZOLINES EN TANT QU'INHIBITEURS DE L'HYDROLASE DES AMIDES D'ACIDES GRAS
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2010135360A1

  公开（公告）日：2010-11-25

  The present invention provides isoxazoline FAAH inhibitors of the formula (I): or pharmaceutically acceptable forms thereof, wherein each of G, Ra, Rb, Rc, and Rd are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I), or pharmaceutically acceptable form thereof, to a subject in need thereof.

  本发明提供了式(I)的异噁唑啉FAAH抑制剂或其药用可接受形式，其中G、Ra、Rb、Rc和Rd中的每一个如本文所定义。本发明还提供了包括式(I)化合物或其药用可接受形式以及药用可接受赋形剂的药物组合物。本发明还提供了治疗FAAH介导疾病的方法，包括向需要的受试者施用式(I)化合物或其药用可接受形式的治疗有效量。
• ISOXAZOLINES AS INHIBITORS OF FATTY ACID AMIDE HYDROLASE
  申请人：INFINITY PHARMACEUTICALS, INC.

  公开号：US20150099738A1

  公开（公告）日：2015-04-09

  The present invention provides isoxazoline FAAH inhibitors of the formula (I): or pharmaceutically acceptable forms thereof, wherein each of G, R a , R b , R c , and R d are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient. The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I), or pharmaceutically acceptable form thereof, to a subject in need thereof.

  本发明提供了式（I）的异噁唑烷FAAH抑制剂或其药学上可接受的形式，其中G、Ra、Rb、Rc和Rd的定义如本文所述。本发明还提供了含有式（I）化合物或其药学上可接受的形式和药学上可接受的载体的制剂。本发明还提供了治疗FAAH介导疾病的方法，包括向需要治疗的受体中投与式（I）化合物或其药学上可接受的形式的治疗有效量。
• US8765735B2
  申请人：——

  公开号：US8765735B2

  公开（公告）日：2014-07-01