氯卓酸 | 23887-31-2

• 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: 氯卓酸
• 英文名称: clorazepate
• 英文别名: Clorazepate；7-chloro-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepine-3-carboxylic acid；7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid；Chlorazepat；7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-4-ium-3-carboxylate
• CAS: 23887-31-2；149128-43-8；149128-44-9
• 化学式: C₁₆H₁₁ClN₂O₃
• 分子量: 314.728
• InChiKey: XDDJGVMJFWAHJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

药物在肝脏中代谢并在尿液中主要排出。主要代谢物去甲地西泮通过羟基化进一步代谢。尿液中的主要代谢物是结合的奥沙西泮（3-羟基去甲地西泮），尿液中还发现了少量的结合的对-羟基去甲地西泮和去甲地西泮。

The drug is metabolized in the liver and excreted primarily in the urine. The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine.

来源:DrugBank

代谢

药物在肝脏中代谢并在尿液中主要排出。主要代谢物去甲安定进一步通过羟基化代谢。尿液中的主要代谢物是结合的奥沙西泮（3-羟基去甲安定），尿液中还发现了少量的结合的对-羟基去甲安定和去甲安定。 消除途径：药物在肝脏中代谢并在尿液中主要排出。 半衰期：血清半衰期约为2天。主要代谢物去甲安定迅速出现在血液中，并从血浆中以大约40到50小时的表观半衰期被消除。

The drug is metabolized in the liver and excreted primarily in the urine. The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine. Route of Elimination: The drug is metabolized in the liver and excreted primarily in the urine. Half Life: The serum half-life is about 2 days. Nordiazepam, the primary metabolite, quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.

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，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 (GABA-A) 受体相耦合，这增强了GABA的效果，通过增加GABA对GABA受体的亲和力。抑制性神经递质GABA结合到该位点时，会打开氯离子通道，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 (GABA_A) 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

• 药物性肝损伤

化合物：氯酸酯

Compound:clorazepate

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：警告和预防措施

Label Section:Warnings and precautions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

口服给药后迅速吸收（生物利用度为91%）。

Rapidly absorbed following oral administration (bioavailability is 91%).

来源:DrugBank

吸收、分配和排泄

• 消除途径

药物在肝脏中代谢并在尿液中主要排出。

The drug is metabolized in the liver and excreted primarily in the urine.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  奥沙唑仑 、 普拉西 、 氯卓酸 生成 去甲西泮
  参考文献：
  名称：

  OCHS, H. R.;GREENBLATT, D. J.;LOCNISKAR, A., J. CLIN. PHARMACOL., 1984, 24, N 10, 446-451

  摘要：

  DOI：

文献信息

• [EN] NITRIC OXIDE RELEASING PRODRUGS OF THERAPEUTIC AGENTS<br/>[FR] PROMÉDICAMENTS D'AGENTS THÉRAPEUTIQUES LIBÉRANT DE L'OXYDE NITRIQUE
  申请人：SATYAM APPARAO

  公开号：WO2014111957A1

  公开（公告）日：2014-07-24

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其中所述药物或治疗剂至少含有一个羧酸基团。发明还涉及制备这些一氧化氮释放前药的方法，包含它们的药物组合物以及使用这些前药的方法。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• Intermediates for preparing 1,4-benzodiazepine-2-ones having a
  申请人：Clin Midy

  公开号：US03966793A1

  公开（公告）日：1976-06-29

  Intermediates for preparing novel benzodiazepines having the formula ##SPC1## In which R.sub.1 is a hydrogen or halogen atom or a trifluoromethyl, loweralkyl, loweralkoxy, nitro or amino group; R.sub.2 is a furyl, a thienyl, cyclohexyl, a loweralkyl group or a phenyl group which may be substituted by a halogen atom or by a trifluoromethyl, nitro, loweralkoxy or loweralkyl group; and R.sub.3 is a hydrogen atom or a loweralkyl group; and R.sub.4 is lowercarbalkoxy, carbamoyl, N-loweralkylcarbamoyl, N,N-diloweralkylcarbamoyl, N-(diloweralkylaminoalkyl)carbamoyl, a group having the formula --COOCat in which Cat is a cation of an alkali metal or a semication of an alkaline earth metal or COOCat.CatOH, said intermediates being ortho-aminoaryl ketimines having the formula ##SPC2## Wherein R is hydrogen or ##EQU1## R.sub.1, R.sub.2, and R.sub.3 are as defined above, R.sub.4 is a hydrogen atom, a lowercarbalkoxy, carbamoyl, N-loweralkylcarbamoyl, N,N-diloweralkylcarbamoyl, N-(diloweralkylaminoalkyl)-carbamoyl, alkyl or substituted alkyl group; and R.sub.5 is a loweralkyl group.

  用于制备具有以下式子的新型苯二氮平类化合物的中间体：##SPC1## 其中R.sub.1是氢原子、卤素原子或三氟甲基、低碳基、低氧基、硝基或氨基基团；R.sub.2是呋喃基、噻吩基、环己基、低碳基或苯基，其可以被卤素原子或三氟甲基、硝基、低碳氧基或低碳基取代；R.sub.3是氢原子或低碳基；R.sub.4是低碳基酯基、氨酰基、N-低碳基氨基甲酰基、N,N-二低碳基氨基甲酰基、N-(二低碳基氨基烷基)氨基甲酰基、具有公式--COOCat的基团，其中Cat是碱金属的阳离子或碱土金属的半阳离子或COOCat.CatOH，这些中间体是具有以下式子的邻氨基芳基酮亚胺：##SPC2## 其中R是氢原子或##EQU1## R.sub.1、R.sub.2和R.sub.3如上所定义，R.sub.4是氢原子、低碳基酯基、氨酰基、N-低碳基氨基甲酰基、N,N-二低碳基氨基甲酰基、N-(二低碳基氨基烷基)氨基甲酰基、烷基或取代烷基；R.sub.5是低碳基。
• Novel compounds with high therapeutic index
  申请人：Chandran Ravi V.

  公开号：US20060241017A1

  公开（公告）日：2006-10-26

  The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

  本发明涉及一种新型治疗化合物，其由氨基酸与具有羟基、氨基、羧基或酰化衍生物的药物或药物结合而成。这些高治疗指数的衍生物与它们所制备的药物具有相同的效用，并且它们具有增强的药理和制药特性。实际上，本发明的新型药物衍生物增强了至少一种治疗品质，如本文所定义。本发明还涉及含有这些化合物的制药组合物。
• Active agent delivery systems and methods for protecting and administering active agents
  申请人：Mickle Travis

  公开号：US20070232529A1

  公开（公告）日：2007-10-04

  The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

  本发明涉及活性物质输送系统，更具体地涉及包含氨基酸（作为单个氨基酸或肽）与活性物质共价连接的组合物以及用于给予共轭活性物质组合物的方法。