苄丝肼 | 322-35-0

• 物质功能分类: 原料药 - 神经系统用药 - 抗震颤麻痹药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 苄丝肼
• 中文别名: 2-氨基-3-羟基-2'-(2,3,4-三羟基苄基)丙酰肼；色拉肼羟苄丝肼；DL-丝氨酰(2,3,4-三羟基苄基)肼盐酸盐；羟苯丝肼；三羟苄基丝氨酰肼；羟苄丝肼；2-氨基-3-羟基-2"-(2,3,4-三羟基苄基)丙酰肼
• 英文名称: benserazide
• 英文别名: (RS)-2-amino-3-hydroxy-N′-(2,3,4-trihydroxybenzyl)propanehydrazide；2-amino-3-hydroxy-N′-(2,3,4-trihydroxybenzyl) propanehydrazide；(RS)-2-amino-3-hydroxy-N-(2,3,4-trihydroxybenzyl)propanehydrazide；D,L-serine 2-(2,3,4-trihydroxybenzyl)hydrazide；beneserazide；2-amino-3-hydroxy-N'-[(2,3,4-trihydroxyphenyl)methyl]propanehydrazide
• CAS: 322-35-0
• 化学式: C₁₀H₁₅N₃O₅
• 分子量: 257.246
• InChiKey: BNQDCRGUHNALGH-UHFFFAOYSA-N

物化性质

• 沸点：
  574.2±50.0 °C(Predicted)
• 密度：
  1.541±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  148
• 氢给体数：
  7
• 氢受体数：
  7

ADMET

代谢

Benserazide在小肠粘膜和肝脏中被羟基化成三羟基苄基肼。三羟基苄基肼是芳香酸脱羧酶的强效抑制剂，人们认为，左旋多巴/本塞拉嗪组合产品中的左旋多巴主要通过这种本塞拉嗪代谢物的方式在很大程度上被保护免受脱羧作用的影响。

Benserazide is hydroxylated to trihydroxybenzylhydrazine in the intestinal mucosa and the liver. Trihydroxybenzylhydrazine is a potent inhibitor of the aromatic acid decarboxylase, and it is believed that the levodopa in a levodopa/benserazide combination product is largely protected against decarboxylation mainly by way of this benserazide metabolite.

来源:DrugBank

毒理性

• 蛋白质结合

Benserazide is observed as experiencing 0% protein binding. 本沙瑞酯观察到蛋白质结合率为0%。

Benserazide is observed as experiencing 0% protein binding.

来源:DrugBank

吸收、分配和排泄

• 吸收

在一项研究中，三名患者通过静脉和口服途径接受了50毫克放射性同位素14C-benserazide。另外三名患者单独口服了50毫克14C-benserazide。比较接受口服和静脉注射14C-benserazide的患者的总放射性时间-血浆浓度曲线表明，66%至74%的给药剂量从胃肠道被吸收。在六名患者中的五名中，口服给药后一小时内检测到放射性活性的血浆浓度峰值。

In a study, three patients were administered 50 mg of radiolabelled 14C-benserazide by both intravenous and oral routes. Three additional patients received oral doses of 50 mg 14C-benserazide alone. Comparison of the time-plasma concentration curves of total radioactivity in the patients receiving oral and intravenous 14C-benserazide indicated that between 66% and 74% of the administered dose was absorbed from the gastrointestinal tract. Peak plasma concentrations of radioactivity were detected one hour after oral administration in five of the six patients.

来源:DrugBank

吸收、分配和排泄

• 消除途径

本沙瑞啶以代谢物的形式迅速经尿液排出，大部分在给药后前6小时内排出，85%的尿液排泄发生在12小时内。放射性标记的14C-本沙瑞啶的消除主要是通过尿液排泄，其中静脉给药剂量的86%至90%在尿液中回收，而口服给药剂量的53%至64%在尿液中检测到。大部分的14C-本沙瑞啶在给药后48小时内主要通过尿液排出。在五到八天内进行的粪便回收研究解释了剩余给药的14C-本沙瑞啶的大部分（约30%）。最终，本沙瑞啶几乎完全通过代谢消除。这些代谢物主要经尿液排出（64%）和在较小程度上经粪便排出（24%）。

Benserazide is rapidly excreted in the urine in the form of metabolites, mostly within the first 6 hours of administration, 85% of urinary excretion occurs within 12 hours. Elimination of radiolabelled 14C-benserazide was primarily by urinary excretion with 86% to 90% of an intravenous dose recovered in the urine while 53% to 64% of an oral dose was detected in the urine. The majority of the 14C-benserazide was ultimately accounted for in the urine within 48 hours after administration. Fecal recovery studies conducted over five to eight days accounted for the majority (about 30%) of the remainder of the administered 14C-benserazide. Ultimately, benserazide is almost entirely eliminated by metabolism. These metabolites are mainly excreted in the urine (64%) and to a smaller extent in the feces (24%).

来源:DrugBank

吸收、分配和排泄

• 分布容积

关于benserazide分布体积的易于获取的数据并不存在。

Readily accessible data regarding the volume of distribution of benserazide is not available.

来源:DrugBank

吸收、分配和排泄

• 清除

关于benserazide清除的数据并不容易获得。

Readily accessible data regarding the clearance of benserazide is not available.

来源:DrugBank

安全信息

• 安全说明：
  S26
• 海关编码：
  2928000090
• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38

制备方法与用途

药代动力学

口服吸收快但不完全，吸收率约为58%，不会透过血脑屏障。药物在肠内代谢，并通过尿液排出，约90%的药物在12小时内被排泄。通常将本品与左旋多巴按1:4的比例配伍使用，用于治疗震颤麻痹症。

不良反应

与左旋多巴合用时可减少副作用，但有时会出现失眠和不安等症状。晚期治疗中可能会出现类似舞蹈病的症状。

制剂与规格

多巴丝肼胶囊（美多巴、Madopa）：每粒含125毫克（左旋多巴100毫克和苄丝肼25毫克，相当于盐酸苄丝肼28.5毫克），以及每粒250毫克（左旋多巴200毫克和苄丝肼50毫克，相当于盐酸苄丝肼57毫克）。

化学性质

米黄色或白色结晶状粉末；可溶于水；熔点为146-148℃。

用途

用于神经药理与生理研究，抑制多巴胺脱羧反应。作为一种外周多巴脱羧酶抑制剂，其作用类似于卡比多巴。

生产方法

以2,3,4-三羟基甲苯和DL-丝氨酰肼盐酸盐为原料进行合成获得。

反应信息

• 作为反应物：
  描述：

  苄丝肼 在 carbon nanotube paste electrode modified with ferrocene 作用下， 以 aq. phosphate buffer 为溶剂， 生成
  参考文献：
  名称：

  Nanostructure-based electrochemical sensor for the voltammetric determination of benserazide, uric acid, and folic acid

  摘要：

  A carbon paste electrode modified with carbon nanotubes and ferrocene was fabricated. An electrochemical study of the modified electrode and an investigation into its efficiency for the electrocatalytic oxidation of benserazide, uric acid and folic acid were undertaken. The electrode was also used to study the electrocatalytic oxidation of benserazide using cyclic voltammetry, chronoamperometry, and square wave voltammetry (SWV). We found that the oxidation of benserazide at the surface of the modified electrode occurs at a potential about 285 mV lower than that of unmodified carbon paste electrode. SWV gave a linear dynamic range from 8.0x10(-7) to 7.0x10(-4) mol/L. The detection limit was 1.0x10(-7) mol/L for benserazide. This modified electrode was used for the determination of benserazide, uric acid, and folic acid in an urine sample. (C) 2013, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/s1872-2067(12)60655-x

文献信息

• [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] COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY<br/>[FR] COMPOSÉS INHIBANT L'ACTIVITÉ ENZYMATIQUE DE LA KINASE À MOTIFS RÉPÉTÉS RICHES EN LEUCINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2014137723A1

  公开（公告）日：2014-09-12

  The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及吲唑类化合物，这些化合物是LRRK2激酶的有效抑制剂，并且在治疗或预防LRRK2激酶参与的疾病，如帕金森病中有用。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗LRRK-2激酶参与的这类疾病中使用这些化合物和组合物。
• [EN] COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY<br/>[FR] COMPOSÉS INHIBANT L'ACTIVITÉ ENZYMATIQUE DE LA KINASE À SÉQUENCE RÉPÉTÉE RICHE EN LEUCINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2014134774A1

  公开（公告）日：2014-09-12

  Disclosed are indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which LRRK2 kinase is involved. Also disclosed are pharmaceutical compositions in the prevention or treatment of such diseases in which LRRK2 kinase is involved.

  揭示了一种indazole化合物，它们是LRRK2激酶的有效抑制剂，并且在涉及LRRK2激酶的疾病的治疗或预防中有用。还揭示了在涉及LRRK2激酶的这类疾病的预防或治疗中使用的药物组合物。
• [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。