N4，N6-二环戊基-2-（甲硫基）-5-硝基-4,6-嘧啶二胺 | 39069-52-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: N4，N6-二环戊基-2-（甲硫基）-5-硝基-4,6-嘧啶二胺
• 英文名称: N,N'-dicyclopentyl-2-methylsulfanyl-5-nitropyrimidine-4,6-diamine
• 英文别名: GS39783；N4,N6-dicyclopentyl-2-(methylthio)-5-nitropyrimidine-4,6-diamine；4-N,6-N-dicyclopentyl-2-methylsulfanyl-5-nitropyrimidine-4,6-diamine
• CAS: 39069-52-8
• 化学式: C₁₅H₂₃N₅O₂S
• 分子量: 337.446
• InChiKey: GSGVDKOCBKBMGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N4，N6-二环戊基-2-（甲硫基）-5-硝基-4,6-嘧啶二胺 在 ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 50.0h， 以42%的产率得到N⁴,N⁶-dicyclopentyl-5-nitropyrimidine-2,4,6-triamine
  参考文献：
  名称：

  Simultaneous activation of muscarinic and GABAB receptors as a bidirectional target for novel antipsychotics

  摘要：

  Recent preclinical studies point to muscarinic and GABA(B) receptors as novel therapeutic targets for the treatment of schizophrenia. This study was aimed to assess the role of muscarinic and GABA(B) receptor interactions in animal models of schizophrenia, using positive allosteric modulators (PAMs) of GABA(B) receptor (GS39783), muscarinic M-4 (VU0152100) and M-5 (VU0238429) receptor, and partial allosteric agonist of M-1 receptor (VU0357017).DOI-induced head twitches, social interaction and novel object recognition tests were used as the models of schizophrenia. Analyses of DOI-induced increases in sEPSCs (spontaneous excitatory postsynaptic currents) were performed as complementary experiments to the DOI-induced head twitch studies. lialoperidol-induced catalepsy and the rotarod test were used to examine the adverse effects of the drugs.All three activators of muscarinic receptors were active in DOI-induced head twitches. When administered together with GS39783 in subeffective doses, only the co-administration of VU0152100 and GS39783 was effective. The combination also reduced the frequency but not the amplitude of DOl-induced 5EPSC5. Neither VU0357017 nor VU0238429 were active in social interaction test when given alone, and also the combination of VU0152100 and GS39783 failed to reverse MK-801-induced deficits observed in this test. All muscarinic activators when administered alone or in combination with GS39783 reversed the MK-801-induced disruption of memory in the novel object recognition test, and their actions were blocked by specific antagonists. None of the tested compounds or their combinations influenced the motor coordination of the animals. The compounds had no effect on haloperidol-induced catalepsy and did not induce catalepsy when administered alone. Pharmacokinetic analysis confirmed lack of possible drug-drug interactions after combined administration of GS39783 with VU0357017 or VU0152100; however, when the drug was co-administered with VU0238429 its ability to pass the blood-brain barrier slightly decreased, suggesting potential drug-drug interactions.Our data show that modulation of cholinergic and GABAergic systems can potentially be beneficial in the treatment of the positive and cognitive symptoms of schizophrenia without inducing the adverse effects typical for presently used antipsychotics.

  DOI：

  10.1016/j.bbr.2018.09.019

文献信息

• NOVEL TRIAZINEDIONE DERIVATIVES AS GABAB RECEPTOR MODULATORS
  申请人：Riguet Eric

  公开号：US20100004246A1

  公开（公告）日：2010-01-07

  The present invention provides novel compounds of formula I wherein W 1 , W 2 , W 3 , W 4 , W 5 , B, X 1 , X 2 , X 3 , X 4 , X 5 , E and L are as defined herein; invention compounds are gamma amino butyrique acid receptor-subtype B (“GABA B ”) positive allosteric modulators (enhancers), which are useful to provide methods of treating or preventing diseases or disorders, including treatment of anxiety, depression, epilepsy, schizophrenia, cognitive disorders, spasticity and skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, neuropathic pain and craving associated with cocaine and nicotine, panic disorder, posttraumatic stress disorders, urge urinary incontinence, gastroesophageal reflux disease, transient lower oesophageal sphincter relaxations, functional gastrointestinal disorders and irritable bowel syndrome.

  本发明提供了式I的新化合物，其中W1、W2、W3、W4、W5、B、X1、X2、X3、X4、X5、E和L的定义如本文所述；发明的化合物是γ-氨基丁酸受体亚型B（“GABAB”）正向变构调节剂（增强剂），可用于提供治疗或预防疾病或疾病的方法，包括焦虑、抑郁、癫痫、精神分裂症、认知障碍、痉挛和骨骼肌肌紧张、脊髓损伤、多发性硬化、肌萎缩性侧索硬化、脑瘫、神经痛和与可卡因和尼古丁相关的渴望、惊恐障碍、创伤后应激障碍、急迫性尿失禁、胃食管反流病、暂时性下食管括约肌松弛、功能性胃肠疾病和肠易激综合征的治疗。
• Novel triazinedione derivatives as GABA-B receptor modulators
  申请人：ADDEX Pharma S.A.

  公开号：EP2662366A1

  公开（公告）日：2013-11-13

  The present invention provides novel compounds of formula I wherein W1, W2, W3, W4, W5, B, X1, X2, X3, X4, X5, E and L are as defined herein; invention compounds are gamma amino butyrique acid receptor-subtype B ("GABAB") positive allosteric modulators (enhancers), which are useful to provide methods of treating or preventing diseases or disorders, including treatment of anxiety, depression, epilepsy, schizophrenia, cognitive disorders, spasticity and skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, neuropathic pain and craving associated with cocaine and nicotine, panic disorder, posttraumatic stress disorders, urge urinary incontinence, gastroesophageal reflux disease, transient lower oesophageal sphincter relaxations, functional gastrointestinal disorders and irritable bowel syndrome.

  本发明提供了式 I 的新型化合物，其中 W1、W2、W3、W4、W5、B、X1、X2、X3、X4、X5、E 和 L 如本文所定义；本发明化合物是γ-氨基丁酸受体亚型 B（"GABAB"）正异位调节剂（增强剂），可用于提供治疗或预防疾病或失调的方法，包括治疗焦虑症、抑郁症、癫痫、精神分裂症、认知障碍、痉挛和骨骼肌僵硬、脊髓损伤、多发性硬化症、肌萎缩症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、多发性硬化症、肌萎缩性脊髓侧索硬化症、脑瘫、神经性疼痛以及与可卡因和尼古丁相关的渴求、恐慌症、创伤后应激障碍、急迫性尿失禁、胃食管反流病、一过性下食管括约肌松弛、功能性胃肠病和肠易激综合征。
• NOVEL TRIAZINEDIONE DERIVATIVES AS GABA-B RECEPTOR MODULATORS
  申请人：Addex Pharma S.A

  公开号：EP2104670B1

  公开（公告）日：2016-02-17
• Compositions and methods for enhancing cognitive function and synaptic plasticity
  申请人：Liu Guosong

  公开号：US20060089335A1

  公开（公告）日：2006-04-27

  The present invention provides compositions and methods for enhancing cognitive function and synaptic plasticity. According to the method, Ca ++ influx into excitatory neurons (nerve cells) is decreased by treatment with a number of different agents including divalent cations (e.g., Mg ++ ), GABA B agonists, GABA A agonists, calcium channel blockers, and/or compounds that decrease action potential firing such as sodium channel blockers. Decreasing Ca ++ influx results in increased synaptic plasticity and enhanced cognitive function. In particular, decreasing Ca ++ influx associated with uncorrelated neural activity results in long-lasting increases in synaptic plasticity and cognitive function. This is achieved by administration of agents that cause a voltage-dependent block of NMDA receptors (e.g., divalent cations such as Mg ++ ) or by administration of GABA B agonists such as baclofen. The invention further provides screening methods useful in identifying compounds that enhance synaptic plasticity and cognitive function.
• US8344138B2
  申请人：——

  公开号：US8344138B2

  公开（公告）日：2013-01-01