匹那西泮 | 52463-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 匹那西泮
• 中文别名: 丙炔安定
• 英文名称: pinazepam
• 英文别名: 7-chloro-2,3-dihydro-5-phenyl-1-propargyl-1H-1,4-benzodiazepine-2-one；7-chloro-1,3-dihydro-1(2-propynyl)-2H-1,4-benzodiazepin-2-one；ZINC00001950；7-chloro-5-phenyl-1-prop-2-ynyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one；7-Chlor-1,2-dihydro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-on；7-chloro-5-phenyl-1-prop-2-ynyl-3H-1,4-benzodiazepin-2-one
• CAS: 52463-83-9
• 化学式: C₁₈H₁₃ClN₂O
• 分子量: 308.767
• InChiKey: MFZOSKPPVCIFMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 毒性总结

苯二氮卓类药物非特异性地与苯二氮卓受体BNZ1结合，后者介导睡眠，以及与BNZ2结合，影响肌肉松弛、抗惊厥活性、运动协调和记忆。由于认为苯二氮卓受体与γ-氨基丁酸-A（GABAA）受体相连，这通过增加GABA对GABA受体的亲和力来增强GABA的效果。抑制性神经递质GABA与该位点的结合打开了氯通道，导致细胞膜超极化，阻止细胞进一步兴奋。

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

一般支持性措施应予以实施，包括静脉输液，并保持气道通畅。低血压可以通过使用去甲肾上腺素或美芬丁胺来对抗。透析的价值有限。氟马西尼（安克塞特）是一种竞争性的苯二氮卓受体拮抗剂，可以用作苯二氮卓类药物过量的解毒剂。特别是，氟马西尼在逆转与苯二氮卓类药物相关的中枢神经系统抑制方面非常有效，但在逆转呼吸抑制方面效果较差。然而，其使用存在争议，因为它有许多禁忌症。长期服用苯二氮卓类药物的患者、服用降低癫痫发作阈值的物质的患者，或有心动过速或癫痫病史的患者禁忌使用。一般来说，医疗观察和支持性护理是治疗苯二氮卓类药物过量的主要手段。尽管苯二氮卓类药物可以被活性炭吸收，但在纯苯二氮卓类药物过量时，使用活性炭进行胃部净化并不有益，因为不良反应的风险往往超过该程序可能带来的任何潜在益处。只有在苯二氮卓类药物与其他可能从净化中受益的药物联合服用时，才建议使用。胃灌洗（胃抽吸）或全肠灌洗也不推荐使用。

General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  匹那西泮 生成 2-Propargylamino-5-chlorbenzophenon
  参考文献：
  名称：

  DE, GIOVANNI N.;CHIAROTTI, M., J. CHROMATOGR.-BIOMED. APPL., 428,(1988) N 2, 321-329

  摘要：

  DOI：
• 作为产物：
  描述：

  3-溴丙炔 、 去甲西泮 生成 匹那西泮
  参考文献：
  名称：

  Novel benzo-fused heterocycles as endothelin antagonisits

  摘要：

  本发明涉及新型苯并杂环化合物及其用作制备药物组成物的活性成分。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为内皮素受体拮抗剂的用途。

  公开号：

  US20050124605A1

文献信息

• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERS, OBSESSIVE-COMPULSIVE DISORDER AND ANXIETY DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE, DE TROUBLES OBSESSIVO-COMPULSIFS ET DE TROUBLES DE L'ANXIÉTÉ
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2018098128A1

  公开（公告）日：2018-05-31

  Disclosed are methods for treating NMDA receptor-mediated disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. NMDA receptor-mediated disorders include autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders.

  揭示了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗NMDA受体介导的疾病的方法。NMDA受体介导的疾病包括自闭症谱系障碍、强迫症和焦虑症。
• [EN] TREATMENT OF ANXIETY DISORDERS AND AUTISM SPECTRUM DISORDERS<br/>[FR] TRAITEMENT DES TROUBLES DE L'ANXIÉTÉ ET DES TROUBLES DU SPECTRE AUTISTIQUE
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2016049048A1

  公开（公告）日：2016-03-31

  Disclosed are methods for treating autism spectrum disorders and/or anxiety disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. Anxiety disorders include agoraphobia (with or without panic disorder), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD).

  本文披露了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗自闭症谱系障碍和/或焦虑障碍的方法。焦虑障碍包括广场恐惧症（伴有或不伴有惊恐障碍）、广泛性焦虑障碍（GAD）、社交焦虑障碍（SAD）、惊恐障碍（PD）、创伤后应激障碍（PTSD）和强迫症（OCD）。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2017023679A1

  公开（公告）日：2017-02-09

  Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

  在某些实施例中提供了一些符合本文所定义的A式化合物，其调节5-HT2C受体的活性。在某些实施例中还提供了一些方法，例如用于体重管理、诱导饱腹感、减少食物摄入，以及预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病理性赌博、奖赏缺乏综合征和性成瘾，强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲症），睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱），尿失禁，精神障碍（包括精神分裂症、厌食症和暴食症），阿尔茨海默病，性功能障碍，勃起功能障碍，癫痫，运动障碍（包括帕金森病和抗精神病药物引起的运动障碍），高血压，血脂异常，非酒精性脂肪肝病，肥胖相关肾脏疾病和睡眠呼吸暂停症。
• New piperidinylamino-thieno[2,3-D] pyrimidine compounds
  申请人：Dhanoa S. Dale

  公开号：US20050222175A1

  公开（公告）日：2005-10-06

  The invention relates to 5-HT receptor antagonists. Novel piperidinylamino-thieno [2,3-d]pyrimidine compounds represented by Formula I, and synthesis and uses thereof for treating diseases mediated directly or indirectly by 5-HT receptors, are disclosed. Such conditions include central nervous system disorders such as pulmonary arterial hypertension, migraine, hypertension, disorders of the gastrointestinal tract, restenosis, asthma, obstructive airway disease, prostatic hyperplasia and priapism, anxiety, depression, schizophrenia, neural injury and stroke. Methods of preparation and novel intermediates and pharmaceutical salts thereof are also provided.

  该发明涉及5-HT受体拮抗剂。公开了由式I表示的新型哌啶基氨基噻吩[2,3-d]嘧啶化合物，以及其合成和用途，用于治疗由5-HT受体直接或间接介导的疾病。这些疾病包括中枢神经系统疾病，如肺动脉高压、偏头痛、高血压、胃肠道疾病、再狭窄、哮喘、阻塞性气道疾病、前列腺增生和勃起功能障碍、焦虑、抑郁症、精神分裂症、神经损伤和中风。还提供了制备方法、新型中间体和药用盐。
• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。

表征谱图