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氟哌啶醇 | 52-86-8

中文名称
氟哌啶醇
中文别名
氟呱啶醇;卤吡醇;1-(4-氟苯基)-4-[4-(4-氯苯基)-4-羟基-1-哌啶基]-1-丁酮;氟哌丁苯;氟哌醇
英文名称
haloperidol
英文别名
4-[4-(p-chlorophenyl)-4-hydroxy-piperidino]-4'-fluorobutyrophenone;4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-1-(4-fluorophenyl)butan-1-one;HAL;4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one
氟哌啶醇化学式
CAS
52-86-8
化学式
C21H23ClFNO2
mdl
——
分子量
375.871
InChiKey
LNEPOXFFQSENCJ-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    152 °C
  • 沸点:
    529.0±50.0 °C(Predicted)
  • 密度:
    1.1820 (estimate)
  • 闪点:
    9℃
  • 溶解度:
    在45%(w/v)aq2-羟丙基-β-环糊精溶解度为:0.39 mg/mL
  • 物理描述:
    Solid
  • 颜色/状态:
    Crystals
  • 蒸汽压力:
    4.8X10-11 mm Hg @ 25 °C /Estimated/
  • 水溶性:
    -4.43
  • 解离常数:
    pKa= 8.66
  • 碰撞截面:
    193.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
  • 保留指数:
    2930;2942;2897;2921;2921;2887;2905;2885;2932;2915.9;2942;2942;2925;2925;2915;2970;2905;2965;2927.5;2916;2950

计算性质

  • 辛醇/水分配系数(LogP):
    3.2
  • 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
Haloperidol在肝脏中广泛代谢,只有大约1%的给药剂量以原型在尿液中排泄。在人类中,haloperidol被生物转化为各种代谢物,包括对氟苯甲酰丙酸4-(4-氯苯基)-4-羟基哌啶、还原的haloperidol、吡啶代谢物和haloperidol葡萄糖苷酸。在定期使用haloperidol治疗的精神病患者中,血浆中haloperidol葡萄糖苷酸的含量在代谢物中是最高的,其次是原型haloperidol、还原的haloperidol和还原的haloperidol葡萄糖苷酸。该药物被认为主要通过哌啶氮的氧化N-脱烷基化代谢,形成苯基碳酸哌啶代谢物(这些似乎是不活跃的),以及通过丁苯酮羰基还原为醇,形成羟基haloperidol。参与haloperidol生物转化的酶包括细胞色素P450(CYP),包括CYP3A4和CYP2D6,羰基还原酶和尿苷磷酸葡萄糖葡萄糖苷转移酶。haloperidol的固有肝清除率主要由葡萄糖苷酸化和haloperidol还原为还原的haloperidol以及CYP介导的氧化作用完成。 在体外细胞色素介导的处置研究中,CYP3A4似乎是负责人类haloperidol代谢的主要酶同型物。还原的haloperidol回氧化为母体化合物的固有清除率、氧化N-脱烷基化和吡啶形成的量级相同。这表明同一个酶系统负责上述三种代谢反应。 在体内人类对haloperidol代谢的研究表明,haloperidol的葡萄糖苷酸化占haloperidol生物转化的50至60%,大约23%的生物转化是通过还原途径。haloperidol生物转化的剩余20至30%将通过N-脱烷基化和吡啶形成。
Haloperidol is extensively metabolised in the liver with only about 1% of the administered dose excreted unchanged in urine. In humans, haloperidol is biotransformed to various metabolites, including p-fluorobenzoylpropionic acid, 4-(4-chlorophenyl)-4-hydroxypiperidine, reduced haloperidol, pyridinium metabolites, and haloperidol glucuronide. In psychiatric patients treated regularly with haloperidol, the concentration of haloperidol glucuronide in plasma is the highest among the metabolites, followed, in rank order, by unchanged haloperidol, reduced haloperidol and reduced haloperidol glucuronide. The drug is thought to be metabolized primarily by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive), and by reduction of the butyrophenone carbonyl to the carbinol, forming _hydroxyhaloperidol_. The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP) including CYP3A4 and CYP2D6, carbonyl reductase and uridine di-phosphoglucose glucuronosyltransferase enzymes. The greatest proportion of the intrinsic hepatic clearance of haloperidol is performed by glucuronidation and followed by the reduction of haloperidol to reduced haloperidol and by CYP-mediated oxidation. In studies of cytochrome-mediated disposition in vitro, CYP3A4 appears to be the major isoform of the enzyme responsible for the metabolism of haloperidol in humans. The intrinsic clearance of the back-oxidation of reduced haloperidol to the parent compound, oxidative N-dealkylation and pyridinium formation are of the same order of magnitude. This suggests that the same enzyme system is responsible for the above three metabolic reactions. In vivo human studies on haloperidol metabolism have shown that the glucuronidation of haloperidol accounts for 50 to 60% of haloperidol biotransformation and that approximately 23% of the biotransformation was accounted for by the reduction pathway. The remaining 20 to 30% ofthe biotransformation of haloperidol would be via N-dealkylation and pyridinium formation.
来源:DrugBank
代谢
尽管尚未明确建立其确切的代谢命运,但看来氟哌啶醇主要在肝脏中代谢。该药物主要通过氧化N-脱烷基化作用代谢,作用于哌啶氮原子,形成苯基碳酸哌啶代谢物(这些似乎是不活跃的),以及通过将丁酰苯酮羰基还原为卡宾醇,形成羟基氟哌啶醇。有限的数据表明,还原代谢物羟基氟哌啶醇具有一些药理活性,但其活性似乎低于氟哌啶醇。大鼠尿液中的代谢物包括对氟苯尿酸、β-对氟苯甲酰丙酸和几种未识别的酸性物质。
Although the exact metabolic fate has not been clearly established, it appears that haloperidol is principally metabolized in the liver. The drug appears to be metabolized principally by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive), and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol. Limited data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be less than that of haloperidol. Urinary metabolites in rats include p-fluorophenaceturic acid, beta-p-fluorobenzoylpropionic acid, and several unidentified acids.
来源:Hazardous Substances Data Bank (HSDB)
代谢
...它通过还原成还原态的氟哌啶醇进行代谢,还原态的氟哌啶醇生物学上是无效的。肠道-肝脏循环的不同程度以及代谢中的种族差异也可能会导致氟哌啶醇处置中观察到的变异性。
... it is metabolized via reduction to reduced haloperidol, which is biologically inactive. Different extents of enterohepatic recycling, and ethnic differences in metabolism, could also account for the observed variability in haloperidol disposition.
来源:Hazardous Substances Data Bank (HSDB)
代谢
涉及的酶在卤芬太尔的生物转化包括细胞色素P450(CYP),碳基还原酶和尿苷磷酸葡萄糖醛酸基转移酶。卤芬太尔固有肝脏清除率的最大比例是通过葡萄糖醛酸化,其次是卤芬太尔还原为还原卤芬太尔和CYP介导的氧化。在CYP介导的处置体外研究中,CYP3A4似乎是负责人类卤芬太尔代谢的主要同种型。还原卤芬太尔逆向氧化为母化合物、氧化N-脱烷基和吡啶形成固有的清除率相同数量级,这表明相同的酶系统负责3个反应。在CYP介导的反应中观察到催化活性的大变异,而在葡萄糖醛酸化和碳基还原途径中似乎只有小的变异。卤芬太尔是CYP3A4的底物,也是CYP2D6的抑制剂和激动剂。
The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP), carbonyl reductase and uridine diphosphoglucose glucuronosyltransferase. The greatest proportion of the intrinsic hepatic clearance of haloperidol is by glucuronidation, followed by the reduction of haloperidol to reduced haloperidol and by CYP-mediated oxidation. In studies of CYP-mediated disposition in vitro, CYP3A4 appears to be the major isoform responsible for the metabolism of haloperidol in humans. The intrinsic clearances of the back-oxidation of reduced haloperidol to the parent compound, oxidative N-dealkylation and pyridinium formation are of the same order of magnitude, suggesting that the same enzyme system is responsible for the 3 reactions. Large variation in the catalytic activity was observed in the CYP-mediated reactions, whereas there appeared to be only small variations in the glucuronidation and carbonyl reduction pathways. Haloperidol is a substrate of CYP3A4 and an inhibitor, as well as a stimulator, of CYP2D6.
来源:Hazardous Substances Data Bank (HSDB)
代谢
活体药代遗传学研究已经表明,氟哌啶醇的代谢和处置可能受到基因决定的多态性CYP2D6活性的调控。然而,这些发现似乎与体外人肝微粒体研究和体内药物相互作用研究的结果相矛盾。对于氟哌啶醇代谢的人种间和药代遗传差异可能解释这些观察结果。
... In vivo pharmacogenetic studies have indicated that the metabolism and disposition of haloperidol may be regulated by genetically determined polymorphic CYP2D6 activity. However, these findings appear to contradict those from studies in vitro with human liver microsomes and from studies of drug interactions in vivo. Interethnic and pharmacogenetic differences in haloperidol metabolism may explain these observations.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 毒性总结
识别:氯丙嗪是一种抗精神病药氯丙嗪是一种合成产品。氯丙嗪是丁酰苯系列主要镇静剂的第一种。氯丙嗪用于管理精神病症状,如精神分裂症和躁狂症。它用于控制儿童和成人图雷特综合症的运动性抽动和发声。它对治疗儿童的严重行为问题,如战斗性、爆发性过度兴奋有效。它还用于管理图雷特综合症、顽固性呃逆和作为镇吐药。人类接触:主要风险和靶器官:严重过量的主要特征是锥体外系反应、低血压、呼吸困难和意识障碍。氯丙嗪主要作为多巴胺拮抗剂。临床效果总结:意识可能下降,进展到昏迷;矛盾的是,一些患者表现出混乱、兴奋和不安。可见颤抖或肌肉抽搐、肌肉痉挛、僵硬和抽搐。锥体外系体征可能包括肌张力障碍,有时严重到影响吞咽或呼吸;斜颈、眼球运动危象和角弓反张。瞳孔可能收缩或扩张。低血压和心动过速很常见。有时可能出现心律失常,包括心室颤动、传导缺陷和心脏骤停。禁忌症:使用氯丙嗪后出现了严重的肌张力障碍反应,特别是在儿童和青少年中。因此,在儿童中应极其谨慎使用。氯丙嗪还可能在患有甲状腺功能亢进的患者和接受治疗的患者中引起严重的神经毒性反应。氯丙嗪在严重的中枢神经系统抑制或由任何原因引起的昏迷状态以及对此药物过敏或患有帕森病的个体中是禁忌的。在晚期妊娠中也禁忌使用,因为新生儿可能会出现肌张力障碍反应。在药物治疗期间不应哺乳。进入途径:口服:这是主要的给药途径。注射:通过静脉和肌肉注射。暴露途径的吸收:氯丙嗪易于从胃肠道吸收。由于肝脏的首过效应,口服给药后的血浆浓度低于肌肉注射后的血浆浓度。氯丙嗪的血浆浓度及其治疗效应在受试者之间存在很大的个体差异。氯丙嗪癸酸酯从注射部位吸收非常缓慢,因此适合作为储库注射。它逐渐释放到血液中,在那里迅速解为氯丙嗪。暴露途径的分布:氯丙嗪非常广泛地与血浆蛋白结合(90%)。它广泛分布在体内,并穿过血脑屏障。暴露途径的生物学半衰期:治疗剂量下的血浆半衰期据报道范围从大约13小时到近40小时(雷诺兹,1989年),平均为20小时。代谢:氯丙嗪在肝脏代谢,代谢途径包括氧化的N-脱烷基化。暴露途径的消除:总系统清除率在儿童中增加,在老年患者中减少。代谢后,氯丙嗪通过尿液、胆汁和粪便排出,有40%的证据表明肠肝循环。大约26%在健康受试者的前5天通过尿液排出,20%的患者在前5天排出;到第三天大约有15%通过粪便排出。完全消除单次口服剂量需要28天。作用方式:药效学:多巴胺受体目前被分类为D-1(刺激腺苷酸环化酶)和D-2(抑制腺苷酸环化酶)。神经安定药阻断了D-1和D-2受体,但比例的重要性尚不清楚。神经安定药的治疗剂量似乎与其对大脑多巴胺D-2受体的亲和力相关。神经安定药还阻断了包括H1和H2组胺、α1和α2肾上腺素能、毒蕈碱和5-羟色胺受体的许多其他受体。毒性:人类数据:在服用20至140毫克/天,一到四天内突然死亡的三例。儿童:一名29个月大的女孩和一名11个月大的男孩分食了265毫克的氯丙嗪,他们出现了嗜睡、低体温、反射亢进、神经肌肉僵硬、步态不稳和意向性震颤。尽管报告了泌乳、闭经、乳房发育过度和阳痿等干扰,但对于大多数患者来说,血清催乳素平升高的临床意义尚不清楚。没有对孕妇使用氯丙嗪的严格对照研究。然而,有报告称,在妊娠早期使用氯丙嗪和其他具有疑似致畸潜能的药物后,观察到肢体畸形的情况。在这些病例中,没有建立因果关系。由于这种经验并不排除氯丙嗪对胎儿的损害可能性;因此,只有在益处清楚地证明了对胎儿的潜在风险时,才应在怀孕期间或可能怀孕的妇女中使用这种药物。相互作用:应避免使用酒精与该药物,因为有可能会产生附加效果和低血压。在接受氯丙嗪治疗的少数患者中,出现了脑病综合征(表现为无力、嗜睡、发热、震颤和
IDENTIFICATION: Haloperidol is an antipsychotic agent. Haloperidol is a synthetic product. Haloperidol is the first of the butyrophenone series of major tranquillizers. Haloperidol is indicated for use in the management of manifestations of psychotic disorders such as schizophrenia and mania. It is indicated for the control of tics and vocal utterances of Tourette's Disorder in children and adults. It is effective for the treatment of severe behaviour problems in children of combative, explosive hyperexcitability. It is also used in the management of Gilles de La Tourette's syndrome, intractable hiccup and as an anti-emetic. HUMAN EXPOSURE: Main risks and target organs: The main features of severe overdosage are extrapyramidal reactions, hypotension, respiratory difficulty and impairment of consciousness. Haloperidol acts mainly as a dopamine antagonist. Summary of clinical effects: Consciousness may be depressed, progressing to coma; paradoxically, some patients manifest confusion, excitement and restlessness. Tremor or muscle twitching, muscle spasm, rigidity and convulsions are seen. Extrapyramidal signs can include dystonia, sometimes severe enough to impair swallowing or breathing; torticollis, oculogyric crises and opisthotonos. The pupils may be constricted or dilated. Hypotension and tachycardia are common. Sometimes there can be cardiac arrhythmias, including ventricular fibrillation, conduction defects and cardiac arrest. Contraindications: Severe dystonic reactions have followed the use of haloperidol, particularly in children and adolescents. It should therefore be used with extreme care in children. Haloperidol may also cause severe neurotoxic reactions in patients with hyperthyroidism and in patients receiving lithium. Haloperidol is contraindicated in severe toxic central nervous system depression or comatose states from any cause and individuals who are hypersensitive to this drug or have Parkinson's disease. Also contraindicated in late pregnancy because of dystonic reaction in the neonate. Infants should not be nursed during drug treatment. Routes of entry: Oral: It is the main route of administration. Parenteral: Through intravenous and intramuscular injection. Absorption by route of exposure: Haloperidol is readily absorbed from the gastrointestinal tract. Owing to the first-pass effect of metabolism in the liver, plasma concentrations following oral administration are lower than those following intramuscular administration. There is wide intersubject variation in plasma concentration of haloperidol and its therapeutic effects. The decanoate ester of haloperidol is very slowly absorbed from the site of injection and is therefore suitable for depot injection. It is gradually released into the bloodstream where it is rapidly hydrolysed to haloperidol. Distribution by route of exposure: Haloperidol is very extensively bound to plasma proteins (90%). It is widely distributed in body and crosses the bloodbrain barrier. Biological half-life by route of exposure: The plasma half-life in therapeutic doses is reported to range from about 13 to nearly 40 hours (Reynolds, 1989), with a mean of 20 hours. Metabolism: Haloperidol is metabolized in the liver and the paths of metabolism include oxidative N-dealkylation. Elimination by route of exposure: This rate of total systemic clearance increases in children and decreases in aged patients. After metabolism, haloperidol is excreted in the urine, via the bile and in the feces, there is evidence of enterohepatic recycling by 40%. About 26% was excreted in the urine by the healthy subjects and 20% by the patients in the first 5 days; by the third day about 15% had been excreted in the feces. It takes 28 days to fully eliminate a single oral dose. Mode of action: Pharmacodynamics: Dopamine receptors currently are classified as D-1(stimulate adenylate cyclase) and D-2(inhibit adenylate cyclase). Neuroleptic drugs block both D-1 and D-2 receptors but the significance of the ratio remains unclear. The therapeutic dose of neuroleptic drug appears to correlate with its affinity for brain dopamine D-2 receptors. Neuroleptic drugs also block a number of other receptors including H1 and H2 histamine, alfa 1 and alfa 2 adrenergic, muscarinic and serotoninergic receptors. Toxicity: Human data: Three cases of sudden death after taking 20 to 140 mg daily for one to four days. Children: A 29-month-old girl and an 11 month old boy who divided 265 mg of haloperidol between them developed lethargy, hypothermia, hyperreflexia, neuromuscular rigidity, unsteady gait and intention tremors. Although disturbances such as galactorrhea, amenorrhea, gynaecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. There are no well controlled studies with haloperidol in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of haloperidol along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to haloperidol; this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus. Interactions: The use of alcohol with this drug should be avoided due to possible additive effects and hypotension. An encephalopathic syndrome (characterised by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leucocytosis, elevated serum enzymes, BUN, and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol. A casual relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combination therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear (Physician's Desk Reference, 1987). Other reported interactions involve the following drugs and adverse effects: Beta-blockers: Severe hypotension or pulmonary arrest. Methyldopa: Dementia, psychomotor retardation, memory impairment and inability to concentrate. Indomethacin: Severe drowsiness and confusion. Main adverse effects: In general, the symptoms of overdose would be an exaggeration of known pharmacological effects and adverse reactions. Anticholinergic side effects and sedation occur less often than with aliphatic phenothiazines, but extrapyramidal reactions are more common. Administration of antidopaminergic and anticholinergics may worsen or bring forward the onset of extrapyramidal effects. Idiosyncratic reaction producing severe drowsiness when used with indomethacin. ANIMAL/PLANT STUDIES: Carcinogenicity: Carcinogenicity studies using oral haloperidol were conducted in Wistar rats and in Albino Swiss mice. In the rat study, survival was less than optimal in all dose groups, reducing the number of rats at risk for developing tumors. However, although a relatively greater number of rats survived to the end of the study in high dose male and female groups, these animals did not have a greater incidence of tumors than control animals. Therefore, although not optimal, this study does suggest the absence of haloperidol related increase in the incidence of neoplasia in rats. In female mice there was a statistically significant increase in mammary gland neoplasia and total tumor incidence; there was a statistically significant increase in pituitary gland neoplasia. In male mice, no statistically significant differences in incidence of total tumors or specific tumor types were noted. Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Teratogenicity: Rodents haloperidol by oral or parenteral routes showed an increase in incidence of resorption, reduced fertility, delayed delivery and pup mortality. No teratogenic effect has been reported in rats, rabbits or dogs at dosages within this range, but cleft palate has been observed in mice. Mutagenicity: No mutagenic potential of haloperidol was found in the Ames Salmonella microsomal activation assay.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 毒性总结
喹硫平的治疗效果的确切机制尚不清楚,但该药物似乎在大脑的皮层下平、中脑和脑干网状结构处抑制中枢神经系统。喹硫平似乎抑制了脑干的上升网状激活系统(可能是通过尾状核),从而中断了间脑和大脑皮层之间的冲动。该药物可能在锥体外系系统中拮抗谷酸酸的作用,并且抑制儿茶酚胺受体的作用也可能有助于喹硫平的作用机制。喹硫平还可能抑制中脑中各种神经递质的再摄取,并显示出强烈的中央抗多巴胺能和微弱的中央抗胆碱能活性。该药物在动物中产生僵直并抑制自发性运动活动和条件性回避行为。喹硫平的抗呕吐作用的确切机制也尚未完全确定,但已经显示该药物通过阻断化学感受器触发区(CTZ)中的多巴胺受体直接影响CTZ。
The precise mechanism whereby the therapeutic effects of haloperidol are produced is not known, but the drug appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation. Haloperidol seems to inhibit the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex. The drug may antagonize the actions of glutamic acid within the extrapyramidal system, and inhibitions of catecholamine receptors may also contribute to haloperidol's mechanism of action. Haloperidol may also inhibit the reuptake of various neurotransmitters in the midbrain, and appears to have a strong central antidopaminergic and weak central anticholinergic activity. The drug produces catalepsy and inhibits spontaneous motor activity and conditioned avoidance behaviours in animals. The exact mechanism of antiemetic action of haloperidol has also not been fully determined, but the drug has been shown to directly affect the chemoreceptor trigger zone (CTZ) through the blocking of dopamine receptors in the CTZ.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 肝毒性
肝脏测试异常在接受长期氯丙嗪治疗的病人中报告发生率为20%,但升高的情况很少超过正常上限的3倍。基转移酶异常通常是轻微的、无症状的且短暂的,即使继续用药也会逆转。由于氯丙嗪导致的临床上明显的急性肝损伤的案例已经有所报告,但它们不常见。黄疸的发作在2到6周内,血清酶升高的模式通常是胆汁淤积性或混合性的。一些病例中报告了过敏反应的迹象(发热、皮疹和嗜酸性粒细胞增多),但它们通常是轻微的且自限性的;自身抗体罕见。
Liver test abnormalities have been reported to occur in 20% of patients on long term therapy with haloperidol, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury have been reported due to haloperidol, but they are uncommon. The onset of jaundice is within 2 to 6 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Signs of hypersensitivity (fever, rash and eosinophilia) have been reported in some cases, but they are usually mild and self-limited; autoantibodies are rare.
来源:LiverTox
毒理性
  • 药物性肝损伤
化合物:氯丙嗪
Compound:haloperidol
来源:Drug Induced Liver Injury Rank (DILIrank) Dataset
毒理性
  • 药物性肝损伤
DILI 注解:较少的药物性肝损伤关注
DILI Annotation:Less-DILI-Concern
来源:Drug Induced Liver Injury Rank (DILIrank) Dataset
吸收、分配和排泄
  • 吸收
氟哌啶醇是一种高度亲脂性的化合物,在人体内广泛代谢,这可能导致其药代动力学在个体之间存在很大的变异性。研究发现,口服给予氟哌啶醇的药代动力学值有很大的差异,达到峰值血浆浓度的时间(tmax)报告为1.7-6.1小时,半衰期(t1/2)报告为14.5-36.7小时,药时曲线下面积(AUC)报告为43.73 μg/L•h [范围14.89-120.96 μg/L•h]。氟哌啶醇口服摄入时从胃肠道吸收良好,然而,首次通过肝脏的代谢会使其口服生物利用度降低至40-75%。肌内给药后,健康个体的达到峰值血浆浓度的时间(tmax)为20分钟,而在精神分裂症患者中为33.8分钟,平均半衰期为20.7小时。肌内给药的生物利用度高于口服给药。 给予氟哌啶醇癸酸酯氟哌啶醇的长效治疗剂型)在芝麻油中,会导致药物缓慢释放,以产生长期效果。注射后大约6天,氟哌啶醇的血浆浓度逐渐上升至峰值,表观半衰期约为21天。在第三次或第四次给药后,达到稳态血浆浓度。
Haloperidol is a highly lipophilic compound and is extensively metabolized in humans, which may cause a large interindividual variability in its pharmacokinetics. Studies have found a wide variance in pharmacokinetic values for orally administered haloperidol with 1.7-6.1 hours reported for time to peak plasma concentration (tmax), 14.5-36.7 hours reported for half-life (t1⁄2), and 43.73 μg/L•h [range 14.89-120.96 μg/L•h] reported for AUC. Haloperidol is well-absorbed from the gastrointestinal tract when ingested orally, however, the first-pass hepatic metabolism decreases its oral bioavailability to 40 - 75%. After intramuscular administration, the time to peak plasma concentration (tmax) is 20 minutes in healthy individuals or 33.8 minutes in patients with schizophrenia, with a mean half-life of 20.7 hours. Bioavailability following intramuscular administration is higher than that for oral administration. Administration of haloperidol decanoate (the depot form of haloperidol for long-term treatment) in sesame oil results in slow release of the drug for long-term effects. The plasma concentrations of haloperidol gradually rise, reaching its peak concentration at about 6 days after the injection, with an apparent half-life of about 21 days. Steady-state plasma concentrations are achieved after the third or fourth dose.
来源:DrugBank
吸收、分配和排泄
  • 消除途径
在放射标记研究中,单次口服给药14C标记的氟哌啶醇后,大约30%的放射性物质通过尿液排出,其中18%以氟哌啶醇葡萄糖苷酸形式排出,这表明氟哌啶醇葡萄糖苷酸是人类尿液中以及血浆中的一个主要代谢物。
In radiolabeling studies, approximately 30% of the radioactivity is excreted in the urine following a single oral administration of 14C-labelled haloperidol, while 18% is excreted in the urine as haloperidol glucuronide, demonstrating that haloperidol glucuronide is a major metabolite in the urine as well as in plasma in humans.
来源:DrugBank
吸收、分配和排泄
  • 分布容积
表观分布容积在9.5-21.7 L/kg之间。这种高分布容积与其亲脂性相符,这也表明它可以在包括血脑屏障在内的各种组织中自由移动。
The apparent volume of distribution was found to range from 9.5-21.7 L/kg. This high volume of distribution is in accordance with its lipophilicity, which also suggests free movement through various tissues including the blood-brain barrier.
来源:DrugBank
吸收、分配和排泄
  • 清除
静脉给药后,血浆或血清清除率(CL)为0.39-0.708 L/h/kg(6.5至11.8 ml/min/kg)。口服给药后,清除率为141.65 L/h(范围41.34至335.80 L/h)。非血管内给药后,氟哌啶醇的清除率范围为0.9-1.5 L/h/kg,然而在CYP2D6酶的弱代谢者中,这一速率会降低。CYP2D6酶活性降低可能导致氟哌啶醇浓度增加。在一项精神分裂症患者的群体药代动力学分析中,氟哌啶醇清除率的患者间变异性(变异系数,%)估计为44%。CYP2D6的遗传多态性已被证明是氟哌啶醇药代动力学患者间变异性的重要来源,可能会影响治疗效果和不良反应的发生率。
Following intravenous administration, the plasma or serum clearance (CL) was found to be 0.39-0.708 L/h/kg (6.5 to 11.8 ml/min/kg). Following oral administration, clearance was found to be 141.65 L/h (range 41.34 to 335.80 L/h). Haloperidol clearance after extravascular administration ranges from 0.9-1.5 l/h/kg, however this rate is reduced in poor metabolizers of C_YP2D6_ enzyme. Reduced CYP2D6 enzyme activity may result in increased concentrations of haloperidol. The inter-subject variability (coefficient of variation, %) in haloperidol clearance was estimated to be 44% in a population pharmacokinetic analysis in patients with schizophrenia. Genetic polymorphism of CYP2D6 has been demonstrated to be an important source of inter-patient variability in the pharmacokinetics of haloperidol and may affect therapeutic response and incidence of adverse effects.
来源:DrugBank
吸收、分配和排泄
Haloperidol从胃肠道吸收良好,但首过肝代谢使口服生物利用度降至40至75%。口服给药后0.5至4小时血清浓度达到峰值。
Haloperidol is well absorbed from the gastrointestinal tract but first-pass hepatic metabolism decreases oral bioavailability to 40 to 75%. Serum concentration peaks 0.5 to 4 hours after an oral dose.
来源:Hazardous Substances Data Bank (HSDB)

安全信息

  • 危险等级:
    6.1(b)
  • 危险品标志:
    T
  • 安全说明:
    S26,S36/37/39,S45,S53
  • 危险类别码:
    R61,R36/37/38,R43,R60,R25
  • WGK Germany:
    3
  • 海关编码:
    2933399090
  • 危险品运输编号:
    UN 2811 6.1/PG 3
  • 危险类别:
    6.1(b)
  • RTECS号:
    EU1575000
  • 包装等级:
    III
  • 危险标志:
    GHS06,GHS08
  • 危险性描述:
    H301,H315,H317,H319,H335,H361
  • 危险性防范说明:
    P261,P280,P301 + P310,P305 + P351 + P338
  • 储存条件:
    应密封避光保存。

SDS

SDS:758c3503e5f25baa6b2cf39fbd1b7caf
查看

模块 1. 化学
1.1 产品标识符
: Haloperidol
产品名称
1.2 鉴别的其他方法
无数据资料
1.3 有关的确定了的物质或混合物的用途和建议不适合的用途
仅用于研发。不作为药品、家庭或其它用途。

模块 2. 危险性概述
2.1 GHS-分类
急性毒性, 经口 (类别 3)
若适用,该化学品满足《危险化学品安全管理条例》 的要求。

模块 16. 其他信息
进一步信息
版权所有:2013 Co. LLC. 公司。许可无限制纸张拷贝,仅限于内部使用。
上述信息视为正确,但不包含所有的信息,仅作为指引使用。本文件中的信息是基于我们目前所知,就正
确的安全提示来说适用于本品。该信息不代表对此产品性质的保证。
参见发票或包装条的反面。
皮肤刺激 (类别 2)
眼睛刺激 (类别 2A)
皮肤过敏 (类别 1)
生殖毒性 (类别 2)
特异性靶器官系统毒性(一次接触) (类别 3)
2.2 GHS 标记要素,包括预防性的陈述
象形图
警示词 危险
危险申明
H301 吞咽会中毒
H315 造成皮肤刺激。
H317 可能导致皮肤过敏反应。
H319 造成严重眼刺激。
H335 可能引起呼吸道刺激。
H361 怀疑对生育能力或胎儿造成伤害。
警告申明
预防措施
P201 在使用前获取特别指示。
P202 在读懂所有安全防范措施之前切勿操作。
P261 避免吸入粉尘/烟/气体/烟雾/蒸气/喷雾.
P264 操作后彻底清洁皮肤。
P270 使用本产品时不要进食、饮或吸烟。
P271 只能在室外或通风良好之处使用。
P272 禁止将污染的工作服带出作业场所。
P280 穿戴防护手套/ 眼保护罩/ 面部保护罩。
事故响应
P301 + P310 如果吞下去了: 立即呼救解毒中心或医生。
P302 + P352 如果皮肤接触:用大量肥皂和清洗。
P304 + P340 如吸入: 将患者移到新鲜空气处休息,并保持呼吸舒畅的姿势。
P305 + P351 + P338 如与眼睛接触,用缓慢温和地冲洗几分钟。如戴隐形眼镜并可方便地取
出,取出隐形眼镜,然后继续冲洗.
P308 + P313 如接触到或有疑虑:求医/ 就诊。
P321 具体处置(见本标签上提供的急救指导)。
P330 漱口。
P333 + P313 如出现皮肤刺激或皮疹:求医/就诊。
P337 + P313 如仍觉眼睛刺激:求医/就诊。
P362 脱掉沾污的衣服,清洗后方可再用。
安全储存
P403 + P233 存放于通风良的地方。 保持容器密闭。
P405 存放处须加锁。
废弃处置
P501 将内容物/ 容器处理到得到批准的废物处理厂。
只限于专业使用者。
2.3 其它危害物 - 无

模块 3. 成分/组成信息
3.1 物 质
: C21H23ClFNO2
分子式
: 375.86 g/mol
分子量
组分 浓度或浓度范围
Haloperidol
<=100%
化学文摘登记号(CAS 52-86-8
No.) 200-155-6
EC-编号

模块 4. 急救措施
4.1 必要的急救措施描述
一般的建议
请教医生。 向到现场的医生出示此安全技术说明书。
吸入
如果吸入,请将患者移到新鲜空气处。 如呼吸停止,进行人工呼吸。 请教医生。
皮肤接触
用肥皂和大量的冲洗。 立即将患者送往医院。 请教医生。
眼睛接触
用大量彻底冲洗至少15分钟并请教医生。
食入
切勿给失去知觉者通过口喂任何东西。 用漱口。 请教医生。
4.2 主要症状和影响,急性和迟发效应
据我们所知,此化学,物理和毒性性质尚未经完整的研究。
4.3 及时的医疗处理和所需的特殊处理的说明和指示
无数据资料

模块 5. 消防措施
5.1 灭火介质
灭火方法及灭火剂
雾,抗乙醇泡沫,干粉或二氧化碳灭火。
5.2 源于此物质或混合物的特别的危害
碳氧化物, 氮氧化物, 氯化氢气体, 氟化氢
5.3 给消防员的建议
如必要的话,戴自给式呼吸器去救火。
5.4 进一步信息
无数据资料

模块 6. 泄露应急处理
6.1 作业人员防护措施、防护装备和应急处置程序
戴呼吸罩。 避免粉尘生成。 避免吸入蒸气、烟雾或气体。 保证充分的通风。 人员疏散到安全区域。
避免吸入粉尘。
6.2 环境保护措施
如能确保安全,可采取措施防止进一步的泄漏或溢出。 不要让产品进入下道。
6.3 泄漏化学品的收容、清除方法及所使用的处置材料
收集和处置时不要产生粉尘。 扫掉和铲掉。 放入合适的封闭的容器中待处理。
6.4 参考其他部分
丢弃处理请参阅第13节。

模块 7. 操作处置与储存
7.1 安全操作的注意事项
避免接触皮肤和眼睛。 避免形成粉尘和气溶胶。
在有粉尘生成的地方,提供合适的排风设备。
7.2 安全储存的条件,包括任何不兼容性
贮存在阴凉处。 使容器保持密闭,储存在干燥通风处。
7.3 特定用途
无数据资料

模块 8. 接触控制和个体防护
8.1 容许浓度
最高容许浓度
没有已知的国家规定的暴露极限。
8.2 暴露控制
适当的技术控制
避免与皮肤、眼睛和衣服接触。 休息前和操作本品后立即洗手。
个体防护设备
眼/面保护
面罩與安全眼鏡请使用经官方标准如NIOSH (美国) 或 EN 166(欧盟) 检测与批准的设备防护眼部。
皮肤保护
戴手套取 手套在使用前必须受检查。
请使用合适的方法脱除手套(不要接触手套外部表面),避免任何皮肤部位接触此产品.
使用后请将被污染过的手套根据相关法律法规和有效的实验室规章程序谨慎处理. 请清洗并吹干双手
所选择的保护手套必须符合EU的89/686/EEC规定和从它衍生出来的EN 376标准。
完全接触
物料: 丁腈橡胶
最小的层厚度 0.11 mm
溶剂渗透时间: 480 min
测试过的物质Dermatril® (KCL 740 / Z677272, 规格 M)
飞溅保护
物料: 丁腈橡胶
最小的层厚度 0.11 mm
溶剂渗透时间: 480 min
测试过的物质Dermatril® (KCL 740 / Z677272, 规格 M)
, 测试方法 EN374
如果以溶剂形式应用或与其它物质混合应用,或在不同于EN
374规定的条件下应用,请与EC批准的手套的供应商联系。
这个推荐只是建议性的,并且务必让熟悉我们客户计划使用的特定情况的工业卫生学专家评估确认才可.
这不应该解释为在提供对任何特定使用情况方法的批准.
身体保护
全套防化学试剂工作服, 防护设备的类型必须根据特定工作场所中的危险物的浓度和数量来选择。
呼吸系统防护
如危险性评测显示需要使用空气净化的防毒面具,请使用全面罩式多功能微粒防毒面具N100型(US
)或P3型(EN
143)防毒面具筒作为工程控制的候补。如果防毒面具是保护的唯一方式,则使用全面罩式送风防毒
面具。 呼吸器使用经过测试并通过政府标准如NIOSH(US)或CEN(EU)的呼吸器和零件。

模块 9. 理化特性
9.1 基本的理化特性的信息
a) 外观与性状
形状: 粉末
颜色: 白色
b) 气味
无数据资料
c) 气味阈值
无数据资料
d) pH值
无数据资料
e) 熔点/凝固点
熔点/凝固点: 150 - 152 °C
f) 沸点、初沸点和沸程
无数据资料
g) 闪点
无数据资料
h) 蒸发速率
无数据资料
i) 易燃性(固体,气体)
无数据资料
j) 高的/低的燃烧性或爆炸性限度 无数据资料
k) 蒸气压
无数据资料
l) 蒸汽密度
无数据资料
m) 密度/相对密度
无数据资料
n) 溶性
无数据资料
o) n-辛醇/分配系数
无数据资料
p) 自燃温度
无数据资料
q) 分解温度
无数据资料
r) 粘度
无数据资料

模块 10. 稳定性和反应活性
10.1 反应性
无数据资料
10.2 稳定性
无数据资料
10.3 危险反应
无数据资料
10.4 应避免的条件
无数据资料
10.5 不相容的物质
强氧化剂
10.6 危险的分解产物
其它分解产物 - 无数据资料

模块 11. 毒理学资料
11.1 毒理学影响的信息
急性毒性
半数致死剂量 (LD50) 经口 - 哺乳动物的 - 80 mg/kg
半数致死剂量 (LD50) 经口 - 小鼠 - 71 mg/kg
半数致死剂量 (LD50) 经口 - 犬 - 90 mg/kg
半数致死剂量 (LD50) 皮下的 - 小鼠 - 41 mg/kg
半数致死剂量 (LD50) 腹膜内的 - 大鼠 - 27 mg/kg
半数致死剂量 (LD50) 腹膜内的 - 小鼠 - 30 mg/kg
半数致死剂量 (LD50) 静脉内的 - 兔子 - 8 mg/kg
半数致死剂量 (LD50) 静脉内的 - 大鼠 - 15 mg/kg
半数致死剂量 (LD50) 静脉内的 - 小鼠 - 13 mg/kg
备注: 行为的:运动失调症 行为的:肌肉僵硬(包括肌肉僵直)
半数致死剂量 (LD50) 静脉内的 - 犬 - 18 mg/kg
半数致死剂量 (LD50) 皮下的 - 大鼠 - 60 mg/kg
半数致死剂量 (LD50) 皮下的 - 猫 - > 2.5 mg/kg
半数致死剂量 (LD50) 皮下的 - 犬 - > 80 mg/kg
半数致死剂量 (LD50) 皮下的 - 猴子 - > 1.25 mg/kg
皮肤刺激或腐蚀
无数据资料
眼睛刺激或腐蚀
无数据资料
呼吸道或皮肤过敏
接触皮肤可引起过敏。
导致光敏。光照会引起过敏反应导致皮肤损伤,表现为晒斑、肿、泡或疹子等不同形式。
生殖细胞致突变性
无数据资料
致癌性
无数据资料
IARC:
此产品中没有大于或等于 0。1%含量的组分被 IARC鉴别为可能的或肯定的人类致癌物。
生殖毒性
可疑人类的生殖毒物
特异性靶器官系统毒性(一次接触)
可能引起呼吸道刺激。
特异性靶器官系统毒性(反复接触)
无数据资料
吸入危险
无数据资料
潜在的健康影响
吸入 吸入可能有害。 引起呼吸道刺激。
摄入 误吞会中毒。
皮肤 通过皮肤吸收可能有害。 造成皮肤刺激。
眼睛 造成严重眼刺激。
接触后的征兆和症状
据我们所知,此化学,物理和毒性性质尚未经完整的研究。
附加说明
化学物质毒性作用登记: 无数据资料

模块 12. 生态学资料
12.1 生态毒性
无数据资料
12.2 持久性和降解性
无数据资料
12.3 潜在的生物累积性
无数据资料
12.4 土壤中的迁移性
无数据资料
12.5 PBT 和 vPvB的结果评价
无数据资料
12.6 其它不良影响
无数据资料

模块 13. 废弃处置
13.1 废物处理方法
产品
将剩余的和不可回收的溶液交给有许可证的公司处理。
与易燃溶剂相溶或者相混合,在备有燃烧后处理和洗刷作用的化学焚化炉中燃烧
受污染的容器和包装
按未用产品处置。

模块 14. 运输信息
14.1 联合国危险货物编号
欧洲陆运危规: 2811 国际海运危规: 2811 国际空运危规: 2811
14.2 联合国运输名称
欧洲陆运危规: TOXIC SOLID, ORGANIC, N.O.S. (Haloperidol)
国际海运危规: TOXIC SOLID, ORGANIC, N.O.S. (Haloperidol)
国际空运危规: Toxic solid, organic, n.o.s. (Haloperidol)
14.3 运输危险类别
欧洲陆运危规: 6.1 国际海运危规: 6.1 国际空运危规: 6.1
14.4 包裹组
欧洲陆运危规: III 国际海运危规: III 国际空运危规: III
14.5 环境危险
欧洲陆运危规: 否 国际海运危规 国际空运危规: 否
海洋污染物(是/否): 否
14.6 对使用者的特别提醒
无数据资料


模块 15 - 法规信息
N/A



制备方法与用途

抗精神病药氟哌啶醇

概述

氟哌啶醇属于丁酰苯类抗精神病药物,又名丁苯哌醇或卤吡醇。它主要用于治疗急性和慢性精神分裂症、躁狂症以及反应性精神病等疾病。此外,对伴有兴奋、躁动、幻觉和妄想等症状的重症精神病也有显著疗效,尤其是急性青光眼及有攻击行为的偏执型精神分裂症患者。由于其心血管系统不良反应较少,也被用于治疗脑器质性精神障碍、焦虑性神经症及老年性精神障碍。

药理作用

氟哌啶醇的药理作用与噻嗪类抗精神病药物类似,通过阻断大脑内的多巴胺受体,抑制多巴胺神经元的功能,并加速和增多脑内多巴胺的转化。这导致其具有良好的抗幻觉妄想及抗兴奋躁动效果;同时,该药对锥体外系多巴胺的作用较强,镇吐作用显著但镇静、阻断肾上腺素受体及胆碱受体作用较弱,需要与其他药物联合使用。

吸收与代谢

氟哌啶醇口服后约有70%被吸收,并具有较高的血浆蛋白结合率。通常在3至6小时达到峰值血药浓度。该药物的半衰期约为21小时,在肝脏内代谢并随尿液排出,少量会分泌入乳汁及通过胆汁排泄。

作用机制

氟哌啶醇通过阻断脑内的多巴胺受体起作用,抑制多巴胺神经元的功能,并加速多巴胺的转化。此外,还能阻断植物神经系统中的α-肾上腺素受体,产生相应的生理影响。

药动学

口服后有70%被吸收,一般在3至6小时或肌内注射10至20分钟后达到峰值血药浓度。药物主要分布在肝脏,少量分布于骨骼肌,并可通过血脑屏障进入大脑。约40%的药物会在5天内通过尿液排出,其中1%为原形药物。

不良反应

氟哌啶醇最常见的副作用是锥体外系症状,如静坐不能、运动障碍、震颤和肌张力异常等。儿童、老年人及有脑病变者更容易出现这些症状。长期大量使用可能导致迟发性运动障碍。少数患者可能出现口干、视力模糊、头晕、乏力、便秘、出汗、抑郁反应、过敏性皮疹、粒细胞减少以及恶性综合征等症状,罕见情况下还会引起高热和心电图异常。

过量与禁忌

过量使用氟哌啶醇可能导致角弓反张、扭转痉挛及抽搐等急性脑病症状。发现超剂量时,可适当应用抗胆碱药物,通常3至7天后会缓解。禁忌症包括心功能不全、基底神经节病变以及孕妇和哺乳期妇女。

生物活性与化学性质

氟哌啶醇是丁酰苯类的抗精神病药,结构中含手性碳原子,右旋体活性更强。该药物为白色或类白色的结晶粉末,熔点在148至149.4℃之间,能溶于氯仿甲醇丙酮等有机溶剂,在中的溶解度较低。

用途

氟哌啶醇作为丁酰苯类抗精神病药中最常用的一种药物,被纳入《国家基本药物目录》。主要用于治疗精神分裂症及其他伴有幻觉、妄想及兴奋等症状的疾病。对于急性和慢性精神分裂症患者的躁狂和幻觉症状具有显著疗效,但对抑郁和淡漠无效。

生产方法

氟哌啶醇可通过4-对氯苯-4-羟基哌(见09670)与γ-代对苯丁酮缩合制得。中间体γ-苯丁酮则由氟苯γ-丁内酯氯化亚砜合成(见09060)。

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
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量
    • 1
    • 2
    • 3
    • 4
    • 5

反应信息

  • 作为反应物:
    描述:
    氟哌啶醇 在 perfluoro-cis-2-n-butyl-3-n-propyloxaziridine 、 HCFC-225ca,cb 作用下, 以 二氯甲烷 为溶剂, 反应 0.33h, 以96%的产率得到顺式/反式-氟哌啶醇N-氧化物
    参考文献:
    名称:
    全氟顺式-2,3-二烷基恶唑烷氧化叔胺和吡啶衍生物的选择性
    摘要:
    当叔胺1在-60℃下与全氟顺式-2,3-二烷基恶唑烷2反应时,高产率地形成相应的N-氧化物3。该过程是化学选择性和非对映选择性的。烯基取代的吡啶反应中的化学选择性取决于溶剂,仅在质子和非质子条件下分别发生在碳-碳双键或氮原子上。当使用标准试剂时,选择性较低。
    DOI:
    10.1016/s0040-4020(98)00417-7
  • 作为产物:
    描述:
    3-[2-(4-fluorophenyl)-[1,3]dioxolan-2-yl]propionic acid methyl ester盐酸二异丁基氢化铝 、 sodium cyanoborohydride 、 溶剂黄146 作用下, 以 四氢呋喃甲醇二氯甲烷 为溶剂, 反应 33.0h, 生成 氟哌啶醇
    参考文献:
    名称:
    室温离子液体中的Stetter反应及其在氟哌啶醇合成中的应用
    摘要:
    咪唑型室温离子液体(RTIL)已用于Stetter反应,以良好的收率提供了所需的1,4-二羰基化合物。噻唑鎓盐和Et 3 N是在离子液体中进行该反应的有效催化剂。已经证明了再循环和再利用溶剂的可能性,尽管不可能再循环噻唑鎓催化剂。该方法用于氟哌啶醇的全合成。
    DOI:
    10.1002/adsc.200404123
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文献信息

  • [EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
    申请人:UNIV TEXAS
    公开号:WO2017007634A1
    公开(公告)日:2017-01-12
    The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.
    所描述的发明提供了用于治疗对胆固醇生物合成抑制作出反应的肿瘤的小分子抗癌化合物。这些化合物选择性地抑制肿瘤来源的癌细胞中的胆固醇生物合成途径,但不影响正常分裂的细胞。
  • [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
    申请人:GILEAD APOLLO LLC
    公开号:WO2017075056A1
    公开(公告)日:2017-05-04
    The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
    本发明提供了化合物I和II,这些化合物可用作乙酰辅酶A羧化酶(ACC)的抑制剂,以及它们的组合物和使用方法。
  • [EN] SUBSTITUTED N-HETEROCYCLIC CARBOXAMIDES AS ACID CERAMIDASE INHIBITORS AND THEIR USE AS MEDICAMENTS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
    申请人:BIAL BIOTECH INVEST INC
    公开号:WO2021055627A1
    公开(公告)日:2021-03-25
    The invention provides substituted N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
    这项发明提供了替代的N-杂环羧酰胺和相关化合物,含有这些化合物的组合物,医疗工具包,以及使用这些化合物和组合物治疗患者的医疗疾病(例如癌症、溶酶体贮积症、神经退行性疾病、炎症性疾病)的方法。
  • [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。
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表征谱图

  • 氢谱
    1HNMR
  • 质谱
    MS
  • 碳谱
    13CNMR
  • 红外
    IR
  • 拉曼
    Raman
hnmr
mass
cnmr
ir
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  • 峰位数据
  • 峰位匹配
  • 表征信息
Shift(ppm)
Intensity
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Assign
Shift(ppm)
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测试频率
样品用量
溶剂
溶剂用量
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