(N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide) | 930478-88-9

• 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-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide)
• 英文别名: N-(3-chloro-2-methylphenyl)quinoxaline-2-carboxamide；N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide
• CAS: 930478-88-9
• 化学式: C₁₆H₁₂ClN₃O
• 分子量: 297.744
• InChiKey: SCIBFCFFUQXLCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  邻苯二胺 在 双氧水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 29.0h， 生成 (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide)
  参考文献：
  名称：

  Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice

  摘要：

  Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic pituitary adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT(3) receptor, 4i was examined on CURT induced depression in mice. CURT (30 mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5-1 mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10 mg/kg), for the last 2-weeks of CURT dosing. Repeated CURT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CURT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CURT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CURT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT(3) antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2015.01.021

文献信息

• Isocyanide Heterodimerization-Triggered Three-Component Reaction: Diversity-Oriented Synthesis of Quinoxalines
  作者：Lan Bao、Min Li、Lianshun Zhang、Yating Xue、Jinhuan Dong、Xianxiu Xu

  DOI：10.1021/acs.orglett.3c00794

  日期：——

  (IMCRs) are usually triggered by addition of the isocyano group to the strong electrophilic component. We herein report a new isocyanide-based three-component reaction, in which an unprecedented quinoxaline-based zwitterionic intermediate is generated from the chemoselective heterodimerization of weak electrophilic ortho-diisocyanoarenes and common isocyanides. This reactive zwitterion could react in situ

  已知的基于异氰化物的多组分反应 (IMCR) 通常是通过将异氰基基团添加到强亲电组分中来触发的。我们在此报道了一种新的基于异氰化物的三组分反应，其中一种前所未有的基于喹喔啉的两性离子中间体是由弱亲电性邻二异氰基芳烃和常见异氰化物的化学选择性异二聚化产生的。这种反应性两性离子可以与各种捕获剂原位反应，以提供一系列结构多样的喹喔啉。
• Design, synthesis and structure–activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression
  作者：Radhakrishnan Mahesh、Thangaraj Devadoss、Dilip Kumar Pandey、Shvetank Bhatt、Shushil Kumar Yadav

  DOI：10.1016/j.bmcl.2010.08.128

  日期：2010.11

  A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC center dot HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds' structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT3 receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT, which was expressed in the form of pA(2) value. All the synthesized compounds showed antagonism towards 5-HT3 receptor; based on this result, a structure-activity relationship was derived, which reveals that the aromatic residue in 5-HT3 receptor antagonists may have hydrophobic interaction with 5-HT3 receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA(2) values exhibited good anti-depressant-like activity as compared to the vehicle-treated group. (C) 2010 Elsevier Ltd. All rights reserved.
• Antidepressant and anti-anxiety like effects of 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist in acute and chronic neurobehavioral rodent models
  作者：Deepali Gupta、Mahesh Radhakrishnan、Devadoss Thangaraj、Yeshwant Kurhe

  DOI：10.1016/j.ejphar.2014.04.008

  日期：2014.7

  Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light-dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chloropheny1)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system. (C) 2014 Elsevier B.V. All rights reserved.
• Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice
  作者：Deepali Gupta、Mahesh Radhakrishnan、Yeshwant Kurhe

  DOI：10.1016/j.steroids.2015.01.021

  日期：2015.4

  Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic pituitary adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT(3) receptor, 4i was examined on CURT induced depression in mice. CURT (30 mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5-1 mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10 mg/kg), for the last 2-weeks of CURT dosing. Repeated CURT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CURT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CURT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CURT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT(3) antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation. (C) 2015 Elsevier Inc. All rights reserved.