A-羟基阿普唑仑 | 37115-43-8

• 物质功能分类: 分析化学 - 标准品 - 标准物质
• 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: A-羟基阿普唑仑
• 中文别名: Α-羟基阿普唑仑；Alpha-羟基阿普唑仑；α-羟基阿普唑仑
• 英文名称: 8-chloro-1-hydroxymethyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine
• 英文别名: α-hydroxyalprazolam；alpha-Hydroxyalprazolam；(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanol
• CAS: 37115-43-8
• 化学式: C₁₇H₁₃ClN₄O
• 分子量: 324.769
• InChiKey: ZURUZYHEEMDQBU-UHFFFAOYSA-N

物化性质

• 熔点：
  129-134°C
• 闪点：
  9℃
• 溶解度：
  溶于二氯甲烷20mg/mL，澄清，无色至淡黄色
• 碰撞截面：
  173.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  3010
• 稳定性/保质期：
  常规情况下不会分解，没有危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• 海关编码：
  2933990090
• 储存条件：
  密封，在0°C下保存

反应信息

• 作为反应物：
  描述：

  A-羟基阿普唑仑 在 乙酸酐 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 生成 1-acetoxymethyl-8-chloro-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine
  参考文献：
  名称：

  Triazolobenzodiazepine derivatives

  摘要：

  6-苯基-4H-s-三唑并[4,3-a][1,4]苯并二氮䓬-1-较低烷醇、它们的醚和酯、1-(氟较低烷基)-6-苯基-4H-s-三唑并[4,3-a][1,4]苯并二氮䓬-5-氧化物及其药学上可接受的酸加合物具有中枢抑制作用，特别是抗攻击和抗惊厥作用，并且是制药组合物的活性成分。具体实施例包括6-苯基-8-氯-4H-s-三唑并[4,3-a][1,4]苯并二氮䓬-1-甲醇和1-(氟甲基)6-苯基-8-氯-4H-s-三唑并[4,3-a][1,4]苯并二氮䓬-1。

  公开号：

  US04427590A1
• 作为产物：
  描述：

  阿普唑仑 在 human hepatocytes 、 Williams' Medium E cell culture medium 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 A-羟基阿普唑仑
  参考文献：
  名称：

  Prediction of metabolic clearance using fresh human hepatocytes: Comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines

  摘要：

  1. Predictions of in vivo intrinsic clearance from cryopreserved human hepatocytes may be systematically low. In the current study, the metabolite kinetics of a series of CYP3A4 substrates (benzodiazepines) in fresh human hepatocytes from five donors, via a major UK supplier, were investigated and compared with those previously reported (by the authors' laboratory) for cryopreserved human hepatocytes and hepatic microsomes.2. A high incidence of autoactivation (up to tenfold) and heteroactivation (by testosterone, up to 14-fold) among the major pathways was observed. CYP capacity (V-max) was marginally lower and 'affinity' constants (K-M, S-50) were marginally greater compared with cryopreserved hepatocytes.3. Average intrinsic clearance (based on maximal clearance, CLmax) was sevenfold lower than in cryopreserved hepatocytes (reflecting sensitivity of intrinsic clearance estimation in vitro to mechanistic parameter values, particularly those involving atypical kinetics), but scaled intrinsic clearances for fresh (and cryopreserved) hepatocytes were within the range previously determined in hepatic microsomes.4. There was no evidence from this series of studies that fresh hepatocytes provide quantitatively improved estimates of intrinsic clearance over cryopreserved hepatocytes.

  DOI：

  10.1080/00498250701834665

文献信息

• Novel synthesis of the pharmacologically important 1-substituted-6-phenyl-4<i>H</i>-<i>s</i>-triazolo[4,3-<i>a</i>][1,4]benzodiazepines
  作者：Jackson B. Hester

  DOI：10.1002/jhet.5570170331

  日期：1980.5

  Several 6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines have useful biological activity both in experimental animals and in man. This manuscript describes a novel synthesis of these compounds from intermediates that do not have a pre-formed benzodiazepine ring system.

  几种6-苯基-4 H - s-三唑并[4,3- a ] [1,4]苯并二氮杂pine在实验动物和人类中均具有有用的生物学活性。该手稿描述了从不具有预先形成的苯并二氮杂ring环系统的中间体新颖合成这些化合物的方法。
• [EN] REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF POUR SPECTROMÉTRIE DE MASSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2020020849A1

  公开（公告）日：2020-01-30

  The present invention relates to reagents which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said reagents.

  本发明涉及适用于质谱的试剂，以及利用所述试剂进行分析物分子的质谱测定方法。
• Preparing 1-(hydroxymethyl)-triazolobenzodiazepines and
  申请人：The Upjohn Company

  公开号：US04501698A1

  公开（公告）日：1985-02-26

  A process is provided for converting 1-hydrogen-triazolo[4,3-a]-[1,4]benzodiazepines, e.g., estazolam, to 1-(hydroxymethyl)-triazolo-[4,3-a][1,4]benzodiazepines, and, if desired, these 1-(hydroxymethyl)-compounds to 1-aminomethyl compounds, e.g., to adinazolam, without the need for column chromatography or sealed tube procedures, and while minimizing 1,4-bis-(hydroxymethyl)- group formation.

  提供一种将1-氢-三唑并[4,3-a]-[1,4]苯二氮杂环己烯，例如恩他唑，转化为1-(羟甲基)-三唑并-[4,3-a][1,4]苯二氮杂环己烯的方法，并且如果需要，将这些1-(羟甲基)化合物转化为1-氨甲基化合物，例如阿地那唑，而无需使用柱层析或密封管程序，并最小化1,4-双-(羟甲基)-基团形成。
• 6-Substituted-11b-phenyl-3,
  申请人：Ciba-Geigy Corporation

  公开号：US03941799A1

  公开（公告）日：1976-03-02

  Compounds of the class of 6-substituted 11b-phenyl-3,11b-oxazirino[2,3-d]-s-triazolo[4,3-a][1,4]benzodiazepines have valuable pharmacological properties and are active ingredients for therapeutic compositions. In particular, these new compounds have an anticonvulsive action and inhibit somatic reflexes. Specific embodiments are 10-chloro-11b-phenyl-3,11bH-oxazirino[2,3-d]-s-triazolo[4,3-a][1,4] benzodiazepine-6-methanol, 10-chloro-11b-phenyl-3,11bH-oxazirino[2,3-d]-s-triazolo[4,3-a][1,4]benzodi azepine-6-carboxaldehyde-diethylacetal and 10-chloro-11b-(o-chlorophenyl)-3,11bH-oxazirino[2,3-d]-s-triazolo[4,3-a][1 ,4]benzodiazepine-6-carboxaldehyde-diethylacetal.

  6-取代的11b-苯基-3,11b-噁唑环[2,3-d]-s-三唑并[4,3-a][1,4]苯二氮平类化合物具有有价值的药理学性质，并且是治疗组合物的活性成分。特别是，这些新化合物具有抗惊厥作用并抑制体反射。具体实施例包括10-氯-11b-苯基-3,11bH-噁唑环[2,3-d]-s-三唑并[4,3-a][1,4]苯二氮平-6-甲醇，10-氯-11b-苯基-3,11bH-噁唑环[2,3-d]-s-三唑并[4,3-a][1,4]苯二氮平-6-羧醛-二乙基缩醛和10-氯-11b-(o-氯苯基)-3,11bH-噁唑环[2,3-d]-s-三唑并[4,3-a][1,4]苯二氮平-6-羧醛-二乙基缩醛。
• Triazolo-benzodiazepines
  申请人：The Upjohn Company

  公开号：US04902794A1

  公开（公告）日：1990-02-20

  1-Substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula (III): ##STR1## wherein R is selected from the group consisting of hydroxy, esters thereof, and alkoxy, in which the alkyl group is of 1 to 3 carbon atoms, inclusive; wherein R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoylamino, and dialkylamino in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are produced by condensing a 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-thione of the formula (I): ##STR2## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are defined as above, with an organic acid hydrazide of the formula (II): ##STR3## wherein R' is selected from the group consisting of hydroxy, and alkoxy defined as above. When R' is hydroxy, esters can be made in conventional manner. The new products of formula III including their pharmacologically acceptable acid addition salts and N-oxides are useful as sedatives, tranquilizers and muscle relaxants in mammals and birds.

  公式（III）的1-取代-6-苯基-4H-s-三唑并[4,3-a][1,4]苯二氮平，其中R选择从羟基，其酯和烷氧基的群体中选择，其中烷基的碳原子为1到3个，包括；其中R1选择从氢和1到3个碳原子的烷基的群体中选择；其中R2，R3，R4和R5选择从羟基，1到3个碳原子的烷基，卤素，硝基，氰基，三氟甲基和烷氧基，烷基硫醚，烷基亚磺酰，烷基磺酰，烷酰胺和双烷基氨基中选择，其中碳链基团为1到3个碳原子，包括；通过将公式（I）的1,3-二氢-5-苯基-2H-1,4-苯二氮平-2-硫酮与公式（II）的有机酸腙缩合而制备。其中，R1，R2，R3，R4和R5如上所定义，R'选择从羟基和如上定义的烷氧基中选择。当R'为羟基时，酯可以以常规方式制备。公式III的新产品包括其药理学上可接受的酸盐和N-氧化物，可用作哺乳动物和鸟类的镇静剂，安定剂和肌肉松弛剂。