N-benzyl-2-azaspiro<4.4>nonane-1,3-dione | 94026-81-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl-2-azaspiro<4.4>nonane-1,3-dione
• 英文别名: 2-benzyl-2-aza-spiro[4.4]nonane-1,3-dione；2-Benzyl-2-azaspiro<4.4>nonan-1,3-dion；2-Benzyl-2-azaspiro[4.4]nonane-1,3-dione
• CAS: 94026-81-0
• 化学式: C₁₅H₁₇NO₂
• mdl: MFCD08448270
• 分子量: 243.305
• InChiKey: AWALATCIPIXAGM-UHFFFAOYSA-N

物化性质

• 熔点：
  63.5 °C(Solv: methanol (67-56-1))
• 沸点：
  452.8±24.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-(羧甲基)环戊烷-1-羧酸 、 苄胺 反应 1.5h， 以65%的产率得到N-benzyl-2-azaspiro<4.4>nonane-1,3-dione
  参考文献：
  名称：

  Synthesis, physicochemical and anticonvulsant properties of N-benzyl and N-aminophenyl derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione. Part I

  摘要：

  To continue our systematic SAR studies, two series of N-benzyl- (X=CH2) and N-aminophenyl- (X=NH) derivatives of 2-azaspiro[4.4]nonane (1a-1j) and 2-azaspiro[4.5]decane-1,3-dione (2a-2j) were synthesized, and evaluated in maximum electroshock seizure (MES), subcutaneous pentylenetetrazole (sc.MET) and rotorod (TOX) tests for their anticonvulsant activity. Among those derivatives, the most potent N-aminophenyl-2-azaspiro[4.4]nonane-1,3-dione 1j had ED50=76.27 mg kg-1. X-ray structures for two pairs of derivatives with a different linker were solved. Then 3-D data for the active 1j versus less active 2j, both having an imine linker (X=NH), and the respective parent of compounds with a methylene linker (X=CH2) (1a and 2a) were discussed.

  DOI：

  10.1016/j.farmac.2005.05.006

文献信息

• 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.
• 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, physicochemical and anticonvulsant properties of N-benzyl and N-aminophenyl derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione. Part I
  作者：Jolanta Obniska、Agnieszka Dzierzawska-Majewska、Agnieszka Zagorska、Pawel Zajdel、Janina Karolak-Wojciechowska

  DOI：10.1016/j.farmac.2005.05.006

  日期：2005.6

  To continue our systematic SAR studies, two series of N-benzyl- (X=CH2) and N-aminophenyl- (X=NH) derivatives of 2-azaspiro[4.4]nonane (1a-1j) and 2-azaspiro[4.5]decane-1,3-dione (2a-2j) were synthesized, and evaluated in maximum electroshock seizure (MES), subcutaneous pentylenetetrazole (sc.MET) and rotorod (TOX) tests for their anticonvulsant activity. Among those derivatives, the most potent N-aminophenyl-2-azaspiro[4.4]nonane-1,3-dione 1j had ED50=76.27 mg kg-1. X-ray structures for two pairs of derivatives with a different linker were solved. Then 3-D data for the active 1j versus less active 2j, both having an imine linker (X=NH), and the respective parent of compounds with a methylene linker (X=CH2) (1a and 2a) were discussed.