溴哌利多 | 10457-90-6

• 物质功能分类: 原料药 - 神经系统用药 - 抗精神病药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 溴哌利多
• 中文别名: 溴哌醇
• 英文名称: bromperidol
• 英文别名: 4-<4-(4-bromophenyl)-4-hydroxypiperidino>-4'-fluorobutyrophenone；bromoperidol；haloperidol；azurene；Impromen；4-[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one
• CAS: 10457-90-6
• 化学式: C₂₁H₂₃BrFNO₂
• mdl: MFCD00866670
• 分子量: 420.322
• InChiKey: RKLNONIVDFXQRX-UHFFFAOYSA-N

物化性质

• 熔点：
  156-158°C
• 沸点：
  215.2°C (rough estimate)
• 密度：
  1.3109 (estimate)
• 溶解度：
  不溶于水
• 碰撞截面：
  194.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 保留指数：
  3023

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

溴哌醇已知的人类代谢物包括4'-氟丁酰苯和4-(4-溴苯基)哌啶-4-醇。

Bromperidol has known human metabolites that include 4'-Fluorobutyrophenone and 4-(4-Bromophenyl)piperidin-4-ol.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• WGK Germany：
  2,3
• RTECS号：
  EU1180000
• 海关编码：
  2933399090
• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料类分开存放。

制备方法与用途

生物活性

Bromperidol (R-11333) 是一种丁酰苯类衍生物，是一种强效且长效的抗精神病试剂，主要用于研究精神分裂症。

类别

有毒物质

毒性分级

高毒

急性毒性

• 口服（大鼠）LD50：359毫克/公斤
• 口服（小鼠）LD50：174毫克/公斤

可燃性危险特性

热分解时释放有毒氮氧化物、溴化物和氟化物烟雾

储运特性

应存放在通风低温干燥的库房中，并与其他食品原料分开存放

灭火剂

水、干粉、干砂、二氧化碳、泡沫或1211灭火剂

反应信息

• 作为反应物：
  描述：

  溴哌利多 在 rat liver microsomes 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 3-(4-氟苯甲酰基)丙酸
  参考文献：
  名称：

  Role of CYP3A in bromperidol metabolism in rat in vitro and in vivo

  摘要：

  1. The aim was to identify whether CYP3A metabolizes bromperidol (BP), an antipsychotic drug, to form 4-fluorobenzoyl-propionic acid (FBPA) in hepatic microsomes from 8-week-old male Sprague-Dawley rats and to investigate whether an inhibitor or an inducer of CYP3A affects BP pharmacokinetics in rat.2. In an in vitro study, only troleandomycin showed marked inhibition of FBPA formation among several specific CYP isozyme inhibitors studied including troleandomycin, diethyldithiocarbamate, furafylline and quinine. Anti-rat CYP3A2 serum inhibited FBPA formation by 80 %, whereas other anti-rat CYP sera (1A1, 1A2, 2B1, 2C11, 2E1) only slightly inhibited it.3. In a pharmacokinetic study, BP half-life was prolonged to 137% of the average control value by 7-day treatment with erythromycin, a CYP3A inhibitor, and shortened to 58 % of the control by 2-day treatment with dexamethasone, a CYP3A inducer. BP clearance was reduced to 68 % of the control by erythromycin and was increased to 145 % of control by dexamethasone.4. These results suggested that BP biotransformation is catalysed mainly by CYP3A to form FBPA in rat and that the modification of this enzyme activity would affect the pharmacokinetics of BP.

  DOI：

  10.1080/004982599238281
• 作为产物：
  描述：

  4-<4-<4-(trimethylstannyl)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone 在 溴 作用下， 以 氯仿 为溶剂， 反应 0.5h， 以79%的产率得到溴哌利多
  参考文献：
  名称：

  Synthesis of high specific activity [75Br]- and [77Br]bromperidol and tissue distribution studies in the rat

  摘要：

  A rapid synthesis of [75Br]- and [77Br]bromperidol with specific activity exceeding 10000 Ci/mmol is described in which a trimethylstannylated analogue of bromperidol is used as a substrate for regiospecific no-carrier-added radiobromination. 4-[4-[4-(Trimethylstannyl)phenyl]-4-hydroxypiperidino]-4'- fluorobutyrophenone was synthesized by the reaction of (trimethylstannyl)sodium with haloperidol and purified by preparative HPLC. Subsequent radiobromination with no-carrier-added 75Br- or 77Br- and in situ oxidation using H2O2/CH3COOH gave a corrected radiochemical yield of 35% with a 30-min preparation time. Tissue distribution studies in the rat show a rapid and prolonged uptake into the brain, liver, and kidneys and consistently low blood concentrations that differ quantitatively from previous studies using relatively low specific activity bromperidol. Potential clinical applications for this high specific activity radiobrominated neuroleptic are discussed.

  DOI：

  10.1021/jm00147a035

文献信息

• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• [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。
• Piperazine derivatives and the use thereof as medicament
  申请人：HOENKE Christoph

  公开号：US20150105397A1

  公开（公告）日：2015-04-16

  The present inventions relate to substituted piperazine derivatives of general formula (I) and to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various medical conditions related to glycine transporter-1 (GlyT1).

  这些发明涉及一般式(I)的取代哌嗪衍生物，以及所述化合物的制备，包括符合一般式(I)的化合物的药物组合物，以及利用这些化合物治疗与甘氨酸转运蛋白-1（GlyT1）相关的各种医疗状况。
• NOVEL COMPOUNDS
  申请人：GRAUERT Matthias

  公开号：US20130184248A1

  公开（公告）日：2013-07-18

  This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R 1 , R 2 , R 3 have meanings given in the description.

  这项发明涉及到式I的化合物，它们作为mGlu5受体活性的正向变构调节剂的用途，含有这些化合物的药物组合物，以及将其用作治疗和/或预防与谷氨酸功能障碍相关的神经和精神疾病，如精神分裂症或认知功能下降，如痴呆症或认知障碍的药剂的方法。A、B、Ar、R1、R2、R3在描述中有给定的含义。