8-(苯基甲氧基)-8-氮杂螺[4.4]壬烷-7,9-二酮 | 131042-61-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 8-(苯基甲氧基)-8-氮杂螺[4.4]壬烷-7,9-二酮
• 英文名称: N-(Benzyloxy)-2-azaspiro(4.4)nonane-1,3-dione
• 英文别名: 2-phenylmethoxy-2-azaspiro[4.4]nonane-1,3-dione
• CAS: 131042-61-0
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: XJFNAMINKUYFCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 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：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-(苯基甲氧基)-8-氮杂螺[4.4]壬烷-7,9-二酮 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 24.5h， 生成
  参考文献：
  名称：

  高效和特异性 ABHD6 抑制剂的设计与合成

  摘要：

  ABHD6 特征模板：我们报道了 ABHD6 的四氢异喹啉和异吲哚啉“特征模板”，对靶标具有个位数的纳摩尔抑制和特异性，以及对丝氨酸水解酶 MGL 和 FAAH 的 >1000 倍选择性。一种 ABHD6 抑制剂减弱了 AMPA 诱导的神经胶质细胞活化，并在大鼠中产生了视网膜神经保护作用。这些新的 ABHD6 抑制剂为开发神经保护以及炎症和糖尿病治疗疗法提供了早期线索。

  DOI：

  10.1002/cmdc.202100406
• 作为产物：
  描述：

  O-苄基羟胺 、 2-噁螺[4.4]壬烷-1,3-二酮 以 甲苯 为溶剂， 反应 0.5h， 以76%的产率得到8-(苯基甲氧基)-8-氮杂螺[4.4]壬烷-7,9-二酮
  参考文献：
  名称：

  Synthesis and anticonvulsant activity of imidooxy derivatives

  摘要：

  Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of > 4.5.

  DOI：

  10.1021/jm00105a059

文献信息

• EDAFIOGHO, IVAN O.;SCOTT, K. R.;MOORE, JACQUELINE A.;FARRAR, VIDA A.;NICH+, J. MED. CHEM., 34,(1991) N, C. 387-392
  作者：EDAFIOGHO, IVAN O.、SCOTT, K. R.、MOORE, JACQUELINE A.、FARRAR, VIDA A.、NICH+

  DOI：——

  日期：——
• Synthesis and calculated log P correlation of imidooxy anticonvulsants
  作者：Vida A. Farrar、M. Ciechanowicz-Rutkowska、J. Grochowski、P. Serda、T. Pilati、G. Filippini、Christine N. Hinko、Afif El-Assadi、Jacqueline A. Moore

  DOI：10.1021/jm00075a005

  日期：1993.11

  Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of >4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss structure activity and the Craig plot analytical approaches as well as a semiempirical method. CLOG P analysis was also applied to this series after experimentally determining the NOR fragment. All compounds were minimized and these physicochemical parameters correlated to anticonvulsant activity. Several interesting substituted benzyloxy compounds emerged from this study: the 2',4'-dichloro (2b), 4'-(trifluoromethyl) (2c), 2'-bromo (2d), 3'-chloro (2o), 2'-chloro (2r), 2'-fluoro (2p), and 3'-fluoro (2w) analogs, all of which had comparable, or better activity than the parent unsubstituted analog (2a). X-ray crystal analysis of the active 2a versus inactive N-benzyl-2-azaspiro[4.4]nonane-1,3-dione (10) is discussed.
• Synthesis and anticonvulsant activity of imidooxy derivatives
  作者：Ivan O. Edafiogho、K. R. Scott、Jacqueline A. Moore、Vida A. Farrar、Jesse M. Nicholson

  DOI：10.1021/jm00105a059

  日期：1991.1

  Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of > 4.5.
• Design and Synthesis of Highly Potent and Specific ABHD6 Inhibitors
  作者：Michael S. Malamas、Manjunath Lamani、Shrouq I. Farah、Khadijah A. Mohammad、Christina Yume Miyabe、Girija Rajarshi、Simiao Wu、Nikolai Zvonok、Honrao Chandrashekhar、JodiAnne Wood、Alexandros Makriyannis

  DOI：10.1002/cmdc.202100406

  日期：——

  isoindoline “signature templates” for ABHD6 with single-digit nanomolar inhibitory and specificity for the target, and >1000-fold selectivity against serine hydrolase MGL and FAAH. One ABHD6 inhibitor attenuated AMPA-induced glia activation and produced retinal neuroprotection in rats. These new ABHD6 inhibitors provide early leads to develop therapeutics for neuroprotection and the treatment of inflammation

  ABHD6 特征模板：我们报道了 ABHD6 的四氢异喹啉和异吲哚啉“特征模板”，对靶标具有个位数的纳摩尔抑制和特异性，以及对丝氨酸水解酶 MGL 和 FAAH 的 >1000 倍选择性。一种 ABHD6 抑制剂减弱了 AMPA 诱导的神经胶质细胞活化，并在大鼠中产生了视网膜神经保护作用。这些新的 ABHD6 抑制剂为开发神经保护以及炎症和糖尿病治疗疗法提供了早期线索。