哈拉西泮 | 23092-17-3

• 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: 哈拉西泮
• 中文别名: 哈拉安定；三氟甲安定；氟乙安定
• 英文名称: halazeapam
• 英文别名: Halazepam；7-chloro-1-(2,2,2-trifluoroethyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one；7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepin-2-one
• CAS: 23092-17-3
• 化学式: C₁₇H₁₂ClF₃N₂O
• 分子量: 352.743
• InChiKey: WYCLKVQLVUQKNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

肝脏的。

Hepatic.

来源:Toxin and Toxin Target Database (T3DB)

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，该受体介导睡眠，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) 受体相偶联，这通过增加GABA对GABA受体的亲和力来增强GABA的效应。GABA与位点的结合打开了氯离子通道，导致细胞膜超极化，防止细胞进一步兴奋。

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 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

• 健康影响

撤退症状包括焦虑、抽搐和可能的死亡。它们会导致言语不清、定向障碍和“醉酒”行为。它们在身体和心理上都具有成瘾性。

Withdrawal symptoms include anxiety, convulsions, and possible death. They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口腔

Oral

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

"Barbs"导致发音不清、定向障碍和“醉酒”行为。它们具有身体和心理上的成瘾性。

"Barbs" cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  哈拉西泮 在 十二羰基三钌 、 C₁₀H₁₆ClNO₂S 、 1,3-双(2,4,6-三甲基苯基)氯化咪唑 、 [双(三氟乙酰氧基)碘]苯 作用下， 反应 48.0h， 以32%的产率得到7-chloro-5-(3-chlorophenyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one
  参考文献：
  名称：

  使用N -chloro-2,10-camphorsultam †的 配体促进的钌催化的芳烃的间位C–H氯化氯化物†

  摘要：

  一种实用的元C-H氯化协议建立经由一个钌（0） -催化的邻-metalation策略。使用Ñ氯2,10-樟脑磺内作为新的氯化剂是用于当前反应和N-杂环卡宾（NHC）的成功是至关重要的配体可以显著增强催化转化的反应性。机理研究表明，可能涉及一个不寻常的带有C-Ru键的邻位氯化的邻位C-H钌接替过程。

  DOI：

  10.1039/c8cc03195a
• 作为产物：
  描述：

  5-氯-2-[(2,2,2-三氟乙基)氨基]二苯甲酮 以 水 、 二甲基亚砜 为溶剂， 生成 哈拉西泮
  参考文献：
  名称：

  Process for the preparation of 1,4-benzodiazepine derivatives

  摘要：

  一种1,4-苯二氮䓬类衍生物，或其药学上可接受的酸盐，化学式如下：其中R₁为氢、卤素、硝基或三氟甲基；R₂和R₃分别为氢、卤素、低碳基或三氟甲基；R₄为低碳基、烯基、三卤代烷基、烷氧基烷基、烯氧基烷基、烷氧基氧基烷基、烷酰氧基烷基、环烷基烷基、烷硫基烷基、烷基砜基烷基或式的基团：其中R₆和R₇分别为低碳基，n为1至4的整数；R₅为氢或低碳基，通过将式的苯甲酮衍生物与式的2-异氰乙酰氯衍生物反应得到。

  公开号：

  US03991048A1

文献信息

• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] NMDA RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS NMDA ET UTILISATIONS DE CEUX-CI
  申请人：CADENT THERAPEUTICS

  公开号：WO2018119374A1

  公开（公告）日：2018-06-28

  Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided. The compounds are contemplated to modulate the NMDA receptor.

  本文披露了部分杂芳化合物及其在治疗神经精神障碍，例如精神分裂症和重度抑郁症中的用途方法。提供了药物组合物和制备杂芳化合物的方法。这些化合物被认为可以调节NMDA受体。

表征谱图