阿地唑仑 | 37115-32-5

• 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: 阿地唑仑
• 中文别名: 阿的纳唑仑
• 英文名称: adinazolam
• 英文别名: 8-chloro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine；1-(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-N,N-dimethylmethanamine
• CAS: 37115-32-5
• 化学式: C₁₉H₁₈ClN₅
• 分子量: 351.838
• InChiKey: GJSLOMWRLALDCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.3
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

该药物主要通过肝脏代谢，形成主要代谢物N-脱甲基阿地那唑仑、α-羟基阿尔普唑仑和艾司唑仑。

The drug primarily undergoes hepatic metabolism to form the main metabolite N-desmethyladinazolam, alpha-hydroxyalprazolam, and estazolam.

来源:DrugBank

代谢

阿迪纳唑仑有人类已知的代谢物，包括N-去甲基阿迪纳唑仑。

Adinazolam has known human metabolites that include N-demethyladinazolam.

来源:NORMAN Suspect List Exchange

制备方法与用途

Adinazolam，商品名Deracyn，是一种苯二氮卓类衍生物，更具体来说是三唑并苯二氮卓（TBZD）。它具有抗焦虑、抗惊厥、镇静和抗抑郁作用。Adinazolam由Jackson B. Hester博士开发，目的是增强阿普唑仑的抗抑郁效果，阿普唑仑也是他研发的。遗憾的是，Adinazolam从未获得FDA批准，也从未面向公众销售。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N,N-Didemethyladinazolam	37115-34-7	C17H14ClN5	323.785
  阿普唑仑	alprazolam	28981-97-7	C17H13ClN4	308.77
  艾司唑仑	estazolam	29975-16-4	C16H11ClN4	294.743
  ——	8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo<4,3-a><1,4>benzodiazepine	39479-72-6	C17H12Cl2N4	343.215
  A-羟基阿普唑仑	8-chloro-1-hydroxymethyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine	37115-43-8	C17H13ClN4O	324.769
  ——	5-Chlor-2-<3-<(dimethylamino)methyl>-5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl>benzophenon	54042-46-5	C27H22ClN5O3	499.956
  ——	5-Chlor-2-<3-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl>benzophenon	54485-85-7	C24H15ClN4O3	442.861

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  N-去甲基阿地唑仑甲磺酸酯	N-Demethyladinazolam	37115-33-6	C18H16ClN5	337.812
  ——	[8-chloro-6-(2-chloro-phenyl)-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-ylmethyl]-dimethyl-amine	37115-38-1	C19H17Cl2N5	386.283
  ——	8-chloro-1,4-bis-(dimethylamino-methyl)-6-phenyl-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine	71616-85-8	C22H25ClN6	408.934
  ——	8-chloro-1-[(dimethylamino)methyl]-5,6-dihydro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine	72874-31-8	C19H20ClN5	353.854

反应信息

• 作为反应物：
  描述：

  阿地唑仑 在 platinum(IV) oxide 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 3.67h， 生成 8-chloro-1-[(dimethylamino)methyl]-5,6-dihydro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine
  参考文献：
  名称：

  1-（氨基烷基）-6-芳基-4-Hs-三唑并[4,3-a] [1,4]苯并二氮杂卓具有抗焦虑和抗抑郁活性。

  摘要：

  已经制备了一系列的1-（氨基烷基）-6-芳基-4H-s-三唑并[4，3-a] [1，4]苯并二氮杂并评估中枢神经系统活性。我们发现该系列的成员在旨在检测抗焦虑和抗抑郁活性的药理学测试系统中具有活性。每种类型的活性可以通过适当的取代基选择独立地变化。

  DOI：

  10.1021/jm00178a009
• 作为产物：
  描述：

  艾司唑仑 以 甲醇 为溶剂， 以68.7%的产率得到阿地唑仑
  参考文献：
  名称：

  Process for the production of

  摘要：

  一种制备1-[(二甲基氨基)甲基]-6-取代-4H-s-三唑并[4,3-a][1,4]苯二氮杂环庚烯的方法，包括将4H-s-三唑并[4,3-a][1,4]苯二氮杂环庚烯与试剂##STR1## 反应，其中X.sup.-表示一价酸的阴离子。

  公开号：

  US04001262A1

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] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2016123576A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  这些发明包括一种抑制受试者中COMT酶的方法，以及式I的化合物或其药用可接受盐，这些化合物在治疗由COMT介导的各种疾病中有用，包括帕金森病和/或精神分裂症。