1-苄基-1,7-二氮杂螺[4.4]壬烷 | 128244-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂螺环衍生物
• 中文名称: 1-苄基-1,7-二氮杂螺[4.4]壬烷
• 中文别名: 1-苄基-1,7-二氮杂螺[4.4]壬烷半草酸盐
• 英文名称: 1-benzyl-1,7-diazaspiro[4,4]nonane
• 英文别名: 1-Benzyl-1,7-diazaspiro[4.4]nonane
• CAS: 128244-01-9
• 化学式: C₁₄H₂₀N₂
• mdl: MFCD09056754
• 分子量: 216.326
• InChiKey: YIZAKHJUGTXWTG-UHFFFAOYSA-N

物化性质

• 沸点：
  328.1±17.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  1-苄基-1,7-二氮杂螺[4.4]壬烷 在 tris-(dibenzylideneacetone)dipalladium(0) 、 甲烷磺酸(2-二环己基膦基-2',4',6'-三-异丙基-1,1'-联苯基)(2'-氨基-1,1'-联苯-2-基)钯(II) 、 potassium tert-butylate 、 氢气 、 potassium carbonate 、 lithium hexamethyldisilazane 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 甲苯 为溶剂， 30.0~1665.0 ℃ 、103.42 kPa 条件下， 反应 64.0h， 生成
  参考文献：
  名称：

  CDK4/6 INHIBITOR

  摘要：

  揭示了一系列作为CDK4/6抑制剂的化合物。具体揭示的是由式(I)代表的化合物，其药用盐或异构体，含有相同化合物的药物组合物，以及在制备治疗癌症药物中的使用。

  公开号：

  US20190315745A1
• 作为产物：
  描述：

  N-苯甲酰基-l-脯氨酸 在 镍 lithium aluminium tetrahydride 、 氯化亚砜 、 四甲基乙二胺 、 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， -78.0~50.0 ℃ 、344.73 kPa 条件下， 反应 98.17h， 生成 1-苄基-1,7-二氮杂螺[4.4]壬烷
  参考文献：
  名称：

  Quinolone antibacterial agents substituted at the 7-position with spiroamines. Synthesis and structure-activity relationships

  摘要：

  A series of fluoroquinolone antibacterials having the 7-position (10-position of pyridobenzoxazines) substituted with 2,7-diazaspiro[4.4]nonane (4b), 1,7-diazaspiro[4.4]nonane (5a), or 2,8-diazaspiro[5.5]undecane (6b) was prepared, and their biological activities were compared with piperazine and pyrrolidine substituted analogues. Most exhibited potent Gram-positive and Gram-negative activity, especially when side chain 4b was N-alkylated.

  DOI：

  10.1021/jm00170a035

文献信息

• [EN] PREPARATION AND ENANTIOMERIC SEPARATION OF 7-(3-PYRIDINYL)-1,7-DIAZASPIRO[4.4] NONANE AND NOVEL SALT FORMS OF THE RACEMATE AND ENANTIOMERS<br/>[FR] PRÉPARATION ET SÉPARATION ÉNANTIOMÉRIQUE DE NONANE DE 7-(3-PYRIDINYL)-1,7-DIAZASPIRO[4.4] ET NOUVELLES FORMES DE SEL DU RACÉMATE ET D'ÉNANTIOMÈRES
  申请人：TARGACEPT INC

  公开号：WO2009091561A1

  公开（公告）日：2009-07-23

  A novel scalable synthesis for the preparation of 7-(3- pyridinyI)- 1,7- diazaspiro[4.4)nonane has been developed, and7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane salts have been formed with succinic acid and oxalic acid. Additionally, 7-(3-pyridinyl)-1,7- diazaspiro[4.4]nonane has been separated into its stereoisomers via resolution with L and D di-p-toluoyltartaric acids, giving (R)- and (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane of high enantiomeric purity. Numerous solid salts of the resulting (R)- and (S)-7-(3-pyridinyl)-1,7- diazaspiro[4.4}nonane have been prepared. Methods for the preparation of the racemic and enantiomeric salts, pharmaceutical compositions comprising such salts, and uses thereof are disclosed. The salts can be administered to patients susceptible to or suffering from conditions and disorders, such as central nervous system disorders, to treat and/or prevent such disorders.

  已开发一种新型可扩展的合成方法，用于制备7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷，并用琥珀酸和草酸形成了7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷盐。此外，通过与L和D二对甲苯甲酰酒石酸进行分离，将7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷分离为其立体异构体，得到高对映纯度的(R)-和(S)-7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷。已制备了大量由(R)-和(S)-7-(3-吡啶基)-1,7-二氮杂螺[4.4]壬烷产生的固体盐。公开了制备外消旋和对映体盐的方法，包括含有这些盐的药物组合物以及其用途。这些盐可用于治疗和/或预防中枢神经系统疾病等疾病和疾病，可向易感患者或患有这些疾病和紊乱的患者施用。
• Preparation and characterization of N-(3-pyridinyl) spirocyclic diamines as ligands for nicotinic acetylcholine receptors
  作者：Kevin B. Sippy、David J. Anderson、William H. Bunnelle、Charles W. Hutchins、Michael R. Schrimpf

  DOI：10.1016/j.bmcl.2009.01.099

  日期：2009.3

  Several N-pyridin-3-yl spirobicyclic diamines, designed as conformationally restricted analogs of tebanicline (ABT-594), were synthesized as novel ligands for nicotinic acetylcholine receptors (nAChR). The spirocyclic compounds exhibited weaker binding affinity, than other constrained analogs in accord with a pharmacophore model. Nevertheless, some (1a, 1b) possessed (partial) agonist potencies comparable

  合成了几种N-吡啶-3-基螺双环二胺，它们被设计为替班尼克的构象受限类似物（ABT-594），作为烟碱乙酰胆碱受体（nAChR）的新型配体。根据药效团模型，螺环化合物比其他约束类似物表现出更弱的结合亲和力。然而，在α4β2亚型中，一些（1a，1b）具有与尼古丁相当的（部分）激动剂效能，但相对于α3β4* nAChR具有极大的选择性。
• MACROCYCLIC PYRIMIDINE DERIVATIVES
  申请人：Liu Huaqing

  公开号：US20090253678A1

  公开（公告）日：2009-10-08

  Macrocyclic pyrimidine compounds, compositions comprising such compounds, methods for making the compounds, and methods of treating and preventing the progression of diseases, conditions, and disorders using such compounds and compositions are described herein.

  本文描述了大环嘧啶化合物、包含此类化合物的组合物、制备此类化合物的方法以及使用此类化合物和组合物治疗和预防疾病、病症和障碍的方法。
• N-aryl diazaspiracyclic compounds and methods of preparation and use thereof
  申请人：Targacept, Inc.

  公开号：US20040067930A1

  公开（公告）日：2004-04-08

  Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本文公开了N-芳基二氮杂螺环化合物、N-杂芳基二氮杂螺环化合物的桥接类似物、以及这些化合物的前药或代谢物的制备和使用方法。芳基可以是五元或六元杂环（杂芳基）。这些化合物和组合物可用于治疗和/或预防各种疾病或障碍，特别是那些以尼古丁胆碱能神经递质功能障碍为特征的障碍，包括涉及神经递质释放的神经调节障碍，例如多巴胺释放。中枢神经系统障碍是另一个可以治疗和/或预防的例子，其特征是正常神经递质释放的改变。这些化合物和组合物也可用于缓解疼痛。这些化合物可以：（i）改变患者的大脑中尼古丁胆碱能受体的数量，（ii）表现出神经保护作用，以及（iii）在有效剂量下，不会导致明显的不良副作用（例如，明显增加血压和心率、对胃肠道的明显负面影响以及对骨骼肌的明显影响等副作用）。
• Use of N-aryl diazaspiracyclic compounds in the treatment of addiction
  申请人：Bhatti S. Balwinder

  公开号：US20060058328A1

  公开（公告）日：2006-03-16

  Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological “reward” process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, without resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本发明涉及用于治疗药物成瘾、尼古丁成瘾和/或肥胖症的化合物、组合物和方法。这些化合物是N-芳基二氮杂螺环化合物、N-杂芳基二氮杂螺环化合物的桥接类似物或这些化合物的前药或代谢物。芳基可以是五元或六元杂环环（杂芳基）。这些化合物能够有效地抑制多巴胺的产生和/或分泌，从而有效地抑制与尼古丁和/或非法药物摄入相关的生理“奖励”过程。这些化合物和组合物可以以有效剂量给予，以抑制多巴胺的释放，而不会导致明显的不良副作用（例如，显著增加血压和心率、对胃肠道产生显著负面影响以及对骨骼肌产生显著影响等副作用）。