匹莫林 | 2152-34-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 匹莫林
• 中文别名: 苯异妥英；培脑灵；2-亚氨基-5-苯基-4-恶唑烷酮；匹吗啉；翠雀它明
• 英文名称: 2-amino-5-phenyl-4-oxazolinone
• 英文别名: Pemolin；pemoline；Pemolina [Italian]；2-imino-5-phenyl-1,3-oxazolidin-4-one
• CAS: 2152-34-3
• 化学式: C₉H₈N₂O₂
• 分子量: 176.175
• InChiKey: NRNCYVBFPDDJNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

pemoline被肝脏代谢。pemoline的代谢物包括pemoline共轭物、pemoline二酮、扁桃酸和未识别的极性化合物。Cylert主要通过肾脏排泄，约50%以原形排泄，只有少量以代谢物形式存在。

Pemoline is metabolized by the liver. Metabolites of pemoline include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar compounds. Cylert is excreted primarily by the kidneys with approximately 50% excreted unchanged and only minor fractions present as metabolites.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别：Pemoline是一种类似安非他命的兴奋剂类药物。Pemoline用于治疗发作性睡病和儿童的过度活跃状态，作为心理、教育和社交措施的辅助治疗，用于安非他命、右旋安非他命和乙基苯丙胺。误用：提高性能和缓解疲劳。滥用：口服或注射滥用非常常见。人体暴露：主要风险和靶器官：急性中枢神经系统刺激、心脏毒性导致的心悸、心律失常、高血压和心血管衰竭。依赖和滥用的高风险。临床效果总结：心血管：心悸、胸痛、心动过速、心律失常和高血压常见；严重中毒时可能出现心血管衰竭。心肌缺血、梗死和心室功能障碍已有描述。中枢神经系统（CNS）：CNS刺激、震颤、不安、烦躁、失眠、活动增多、头痛、惊厥、昏迷和高反射已有描述。中风和脑动脉炎已有观察。胃肠道：可能出现呕吐、腹泻和痉挛。泌尿生殖系统：膀胱括约肌张力增加可能导致排尿困难、犹豫和急性尿潴留。肾衰竭可由脱水或横纹肌溶解引起。可能注意到肾缺血。皮肤科：皮肤通常苍白和多汗，但粘膜看起来干燥。内分泌：可能出现短暂的甲状腺素血症。代谢：增加的代谢和肌肉活动可能导致过度通气和体温升高。慢性使用时体重减轻常见。液体/电解质：报告了低钾血症和高钾血症。脱水常见。肌肉骨骼：可能注意到肌束颤动和僵直。精神科：烦躁、混乱、情绪高涨、清醒、健谈、易怒和恐慌发作是典型的。慢性滥用可导致幻觉和偏执。突然停止慢性使用后会出现戒断综合征。暴露途径：口服：从胃肠道的吸收和颊粘膜吸收。对单胺氧化酶的代谢有抗性。吸入：迅速通过吸入吸收，并且通过这种途径滥用。parenteral：在滥用情况下常见的进入途径。暴露途径的吸收：安非他命口服摄入后迅速吸收。血浆峰值浓度在1到3小时内，因身体活动程度和胃中食物量而异。通常在4到6小时内吸收完全。持续释放制剂作为树脂结合的，而不是可溶的盐。与标准安非他命制剂相比，这些化合物显示出较低的血浆峰值浓度，但总吸收量和达到峰值的时间相似。暴露途径的分布：集中在肾脏、肺、脑脊液和大脑中。它们高度脂溶，容易穿过血脑屏障。蛋白结合和分布容积差异很大，但平均分布容积为5 L/kg体重。暴露途径的生物学半衰期：正常条件下，约30%以原形从尿液排出，但这种排泄高度可变，并取决于尿液的pH值。当尿液pH值为酸性（pH 5.5至6.0）时，主要通过尿液排泄，大约60%的剂量在48小时内以原形从肾脏排出。当尿液pH值为碱性（pH 7.5至8.0）时，主要通过脱氨（尿液中原形排泄小于7%）消除；半衰期从16小时到31小时不等。代谢：安非他命的主要代谢途径是通过细胞色素P450脱氨生成对羟基安非他命和苯乙酮；后者进一步氧化生成苯甲酸，并作为葡萄糖苷酸或甘氨酸（马尿酸）结合物排出。较小量的安非他命通过氧化转化为去甲麻黄碱。羟基化产生一个活性代谢物，O-羟基去甲麻黄碱，它作为一种假神经递质，可能解释一些药物效果，特别是在慢性使用者中。消除和排泄：通常在24小时内，治疗剂量的5%到30%以原形从尿液排出，但实际尿排泄和代谢量高度依赖于pH值。作用方式：主要通过在中枢神经系统中引起生物胺（尤其是去甲肾上腺素和多巴胺）的释放来发挥其大部分或全部作用，从神经末梢的储存位点。它还可能通过抑制单胺氧化酶来减缓儿茶酚胺的代谢。毒性：成人：由于个体差异和耐受性的发展，毒性剂量差异很大。儿童：儿童似乎比成人更敏感，不太可能已经发展了耐受性。致畸性：安非他命型化合物通常不像是人类致畸剂。新生儿可能出现轻微的戒断症状，但对婴儿的随访研究并未显示出长期后遗症，尽管需要更多此类研究。非法的母亲使用或滥用对胎儿和新生儿构成重大风险，包括宫内生长迟缓、早产和增加母体、胎儿和新生儿发病的风险。这些不良结果可能是多因素的，涉及多种药物使用、生活方式和母亲健康状况差。然而，在子宫内暴露的新生儿中出现的大脑损伤似乎与血管收缩性质直接相关。智力、心理功能、生长和身体健康在八岁时都在正常范围内，但那些在整个怀孕期间暴露的人倾向于更具侵略性。相互作用：乙酰唑胺

IDENTIFICATION: Pemoline is an amphetamine type psychostimulant drug.Pemoline is used to treat narcolepsy and hyperkinetic states in children as an adjunct to psychological, educational and social measures for amphetamine, dextroamphetamine and ethylphenidate. Misuse: Performance enhancement and relief of fatigue. Abuse: Abuse either orally or by injection is extremely common. HUMAN EXPOSURE: Main risks and target organs: Acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Summary of clinical effects: Cardiovascular: Palpitation, chest pain, tachycardia, arrhythmias and hypertension are common; cardiovascular collapse can occur in severe poisoning. Myocardial ischemia, infarction and ventricular dysfunction are described. Central Nervous System (CNS): Stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia are described. Stroke and cerebral vasculitis have been observed. Gastrointestinal: Vomiting, diarrhea and cramps may occur. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Dermatologic: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Endocrine: Transient hyperthyroxinemia may be noted. Metabolism: Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Fluid/Electrolyte: Hypo- and hyperkalemia have been reported. Dehydration is common. Musculoskeletal: Fasciculations and rigidity may be noted. Psychiatric: Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Routes of exposure: Oral: Readily absorbed from the gastro-intestinal tract and buccal mucosa. It is resistant to metabolism by monoamine oxidase. Inhalation: Rapidly absorbed by inhalation and is abused by this route. Parenteral: Frequent route of entry in abuse situations. Absorption by route of exposure: Amphetamine is rapidly absorbed after oral ingestion. Peak plasma levels occur within 1 to 3 hours, varying with the degree of physical activity and the amount of food in the stomach. Absorption is usually complete by 4 to 6 hours. Sustained release preparations are available as resin-bound, rather than soluble, salts. These compounds display reduced peak blood levels compared with standard amphetamine preparations, but total amount absorbed and time to peak levels remain similar. Distribution by route of exposure: Concentrated in the kidney, lungs, cerebrospinal fluid and brain. They are highly lipid soluble and readily cross the blood-brain barrier. Protein binding and volume of distribution varies widely, but the average volume of distribution is 5 L/kg body weight. Biological half-life by route of exposure: Under normal conditions, about 30% is excreted unchanged in the urine but this excretion is highly variable and is dependent on urinary pH. When the urinary pH is acidic (pH 5.5 to 6.0), elimination is predominantly by urinary excretion with approximately 60% of a dose being excreted unchanged by the kidney within 48 hours. When the urinary pH is alkaline (pH 7.5 to 8.0), elimination is predominantly by deamination (less than 7% excreted unchanged in the urine); the half-life ranging from 16 to 31 hours. Metabolism: The major metabolic pathway for amphetamine involves deamination by cytochrome P450 to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidized to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation. Hydroxylation produces an active metabolite, O-hyroxynorephedrine, which acts as a false neurotransmitter and may account for some drug effect, especially in chronic users. Elimination and excretion: Normally 5 to 30% of a therapeutic dose is excreted unchanged in the urine by 24 hours, but the actual amount of urinary excretion and metabolism is highly pH dependent. Mode of action: Appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especialy norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Toxicity: Adults: The toxic dose varies considerably due to individual variations and the development of tolerance. Children: Children appear to be more susceptible than adults and are less likely to have developed tolerance. Teratogenicity: Amphetamine type compounds generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow up have not shown long term sequelae, although more studies of this nature are needed. Illicit maternal use or abuse presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. These poor outcomes are probably multifactorial in origin, involving multiple drug use, life-styles and poor maternal health. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. Interactions: Acetazolamide: administration may increase serum concentration. Alcohol: may increase serum concentration. Ascorbic acid: lowering urinary pH, may enhance excretion. Furazolidone: May induce a hypertensive response in patients taking furazolidone. Guanethidine: Inhibits the antihypertensive response to guanethidine. Haloperidol: limited evidence indicates that haloperidol may inhibit the effects but the clinical importance of this interaction is not established. Lithium carbonate: isolated case reports indicate that lithium may inhibit the effects. Monoamine oxidase inhibitor: severe hypertensive reactions have followed the administration to patients taking monoamine oxidase inhibitors. Noradrenaline: abuse may enhance the pressor response to noradrenaline. Phenothiazines: may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect. Sodium bicarbonate: large doses of sodium bicarbonate inhibit the elimination, thus increasing the Tricyclic antidepressants: theoretically increases the effect, but clinical evidence is lacking. Clinical effects: Acute poisoning: Ingestion: Effects are most marked on the central nervous system, cardiovascular system, and muscles. The triad of hyperactivity, hyperpyrexia, and hypertension is characteristic of acute overdosage. Agitation, confusion, headache, delirium, and hallucination, can be followed by coma, intracranial hemorrhage, stroke, and death. Chest pain, palpitation, hypertension, tachycardia, atrial and ventricular arrhythmia, and myocardial infarction can occur. Muscle contraction, bruxism (jaw-grinding), trismus (jaw clenching), fasciculation, rhabdomyolysis, are seen leading to renal failure; and flushing, sweating, and hyperpyrexia can all occur. Hyperpyrexia can cause disseminated intravascular coagulation. Inhalation: The clinical effects are similar to those after ingestion, but occur more rapidly. Parenteral exposure: Intravenous injection is a common mode of administration by abusers. The euphoria produced is more intense, leading to a rush or flash which is compared to sexual orgasm. Other clinical effects are similar to those observed after ingestion, but occur more rapidly. Chronic poisoning: Ingestion: Tolerance to the euphoric effects and CNS stimulation induced by such drugs develops rapidly, leading abusers to use larger and larger amounts to attain and sustain the desired affect. Habitual use or chronic abuse usually results in toxic psychosis classically characterized by paranoia, delusions and hallucinations, which are usually visual, tactile or olfactory in nature, in contrast to the typical auditory hallucinations of schizophrenia. The individual may act on the delusions, resulting in bizarre violent behavior, hostility and aggression, sometimes leading to suicidal or homicidal actions. Dyskinesia, compulsive behavior and impaired performance are common in chronic abusers. The chronic abuser presents as a restless, garrulous, tremulous individual who is suspicious and anxious. Course, prognosis, cause of death: Symptoms and signs give a clinical guide to the severity of intoxication as follows: Mild toxicity: restlessness, irritability, insomnia, tremor, hyperreflexia, sweating, dilated pupils, flushing; Moderate toxicity: hyperactivity, confusion, hypertension, tachypnea, tachycardia, mild fever, sweating; Severe toxicity: delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, circulatory collapse. Death can be due to intracranial hemorrhage, acute heart failure or arrhythmia, hyperpyrexia, rhabdomyolysis and consequent hyperkalemia or renal failure, and to violence related to the psychiatric effects. Systematic description of clinical effects: Cardiovascular: Cardiovascular symptoms of acute poisoning include palpitation and chest pain. Tachycardia and hypertension are common. One third of patients had a blood pressure greater than 140/90 mmHg, and nearly two-thirds had a pulse rate above 100 beats per minute. Severe poisoning can cause acute myocardial ischemia, myocardial infarction, and left ventricular failure. These probably result from vasospasm, perhaps at sites of existing atherosclerosis. In at least one case, thrombus was demonstrated initially. Chronic oral abuse can cause a chronic cardiomyopathy; an acute cardiomyopathy has also been described. Hypertensive stroke is a well recognized complication of poisoning. Intra-arterial injection can cause severe burning pain, vasospasm, and gangrene. Respiratory: Pulmonary fibrosis, right ventricular hypertrophy and pulmonary hypertension are frequently found at post-mortem examination. Pulmonary function tests usually are normal except for the carbon monoxide diffusing capacity. Respiratory complications are sometimes caused by fillers or adulterants used in injections by chronic inhalation abusers. These can cause multiple microemboli to the lung, which can lead to restrictive lung disease. Pneumomediastinum has been reported after inhalation. Neurological: Central nervous system (CNS): Main symptoms include agitation, confusion, delirium, hallucinations, dizziness, dyskinesia, hyperactivity, muscle fasciculation and rigidity, rigors, tics, tremors, seizures and coma. Both occlusive and hemorrhagic strokes have been reported after abuse. Twenty-one of 73 drug using young persons with stroke had taken amphetamine, of whom six had documented intracerebral hemorrhage and two had subarachnoid hemorrhage. Patients with underlying arteriovenous malformations may be at particular risk. Stroke can occur after oral, intravenous, or nasal administration. Severe headache beginning within minutes of ingestion is usually the first symptom. In more than half the cases, hypertension which is sometimes extreme, accompanies other symptoms. A Cerebral vasculitis has also been observed. Dystonia and dyskinesia can occur, even with therapeutic dosages. Psychiatric effects, particularly euphoria and excitement, are the motives for abuse. Paranoia and a psychiatric syndrome indistinguishable from schizophrenia are sequelae of chronic use. Autonomic nervous system: Stimulation of alpha-adrenergic receptors produces mydriasis, increased metabolic rate, diaphoresis, increased sphincter tone, peripheral vasoconstriction and decreased gastrointestinal motility. Stimulation of ß-adrenergic receptors produces increased heart rate and contractility, increased automaticity and dilatation of bronchioles. Skeletal and smooth muscle: Myalgia, muscle tenderness, muscle contractions, and rhabdomyolysis, leading to fever, circulatory collapse, and myoglobinuric renal failure, can occur. Gastrointestinal: Most common symptoms are nausea, vomiting, diarrhea, and abdominal cramps. Anorexia may be severe. Epigastric pain and hematemesis have been described after intravenous use. A case of ischemic colitis with normal mesenteric arteriography in a patient taking dexamphetamine has been described. Hepatic: Hepatitis and fatal acute hepatic necrosis have been described. Urinary Renal: Renal failure, secondary to dehydration or rhabdomyolysis may be observed.Other: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. This effect may be a direct result of peripheral alpha-agonist activity. Spontaneous rupture of the bladder has been described in a young woman who took alcohol and an amphetamine containing diet tablet. Endocrine and reproductive systems: Transient hyperthyroxinemia may result from heavy amphetamine use. Dermatological: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Chronic users may display skin lesion, abscesses, ulcers, cellulitis or necrotising angiitis due to physical insult to skin, or dermatologic signs of dietary deficiencies, e.g. cheilosis, purpura. Eye, ear, nose, throat: local effects: Mydriasis may be noted. Diffuse hair loss may be noted and chronic users may display signs of dietary deficiencies. Hematological: Disseminated intravascular coagulation is an important consequence of severe poisoning. Idiopathic thrombocytopenic purpura may occur. Fluid and electrolyte disturbance: Increase metabolic and muscular activity may result in dehydration. Special risks: A case report describes a normal female infant born to mother who took dexamphetamine for narcolepsy throughout pregnancy. Breast-feeding: Amphetamine is passed into breast milk and measurable amounts can be detected in breast-fed infant's urine. Therefore lactating mothers are advised not to take or use these drugs. Other: Withdrawal syndrome: Abrupt discontinuance following chronic use is characterized by apathy, depression, lethargy, anxiety and sleep disturbances. Myalgias, abdominal pain, voracious appetite and a profound depression with suicidal tendencies may complicate the immediate post-withdrawal period and peak in 2 to 3 days. To relieve these symptoms, the user will often return to use more, often at increasing doses due to the tolerance which is readily established. Thus a cycle of use withdrawal use is established. Physical effects here are not life threatening but can lead to a stuporose state; the associated depression can lead to suicide. It may take up to eight weeks for suppressed REM (rapid eye movement) sleep to return to normal. Overamped: When the intravenous dosage is increased too rapidly the individual develops a peculiar condition referred to as overamped: in which he or she is conscious but unable to speak or move. Elevated blood pressure, temperature and pulse as well as chest distress occurs in this setting. Death from overdose in tolerant individuals is infrequent.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物：匹莫林

Compound:pemoline

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

药物性肝损伤标注：最令人关注的药物性肝损伤

DILI Annotation:Most-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：8

Severity Grade:8

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：已撤回

Label Section:Withdrawn

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

pemoline 从消化道迅速吸收

Pemoline is rapidly absorbed from the gastrointestinal tract

来源:DrugBank

吸收、分配和排泄

• 消除途径

Pemoline主要通过肾脏排泄，大约有50%以原形排泄，只有少量以代谢物的形式存在。

Pemoline is excreted primarily by the kidneys with approximately 50% excreted unchanged and only minor fractions present as metabolites.

来源:DrugBank

吸收、分配和排泄

pemoline从胃肠道被迅速吸收。大约50%与血浆蛋白结合。pemoline的血清半衰期约为12小时。服用单剂量的药物后，2到4小时内达到峰值血清水平。在成人中进行的多个剂量的研究表明，稳态在大约2到3天内达到。在给予放射性标记的pemoline的动物中，药物在组织中广泛且均匀分布，包括大脑。

Pemoline is rapidly absorbed from the gastrointestinal tract. Approximately 50% is bound to plasma proteins. The serum half-life of pemoline is approximately 12 hours. Peak serum levels of the drug occur within 2 to 4 hours after ingestion of a single dose. Multiple dose studies in adults at several dose levels indicate that steady state is reached in approximately 2 to 3 days. In animals given radiolabeled pemoline, the drug was widely and uniformly distributed throughout the tissues, including the brain.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 哌甲酯及其代谢物主要通过尿液排泄；只有微不足道的量通过粪便排泄。大约75%的口服剂量在24小时内通过尿液排出；大约43%以原形排出，大约22%以哌甲酯结合物形式排出。

... Pemoline and its metabolites are excreted primarily in urine; only negligible amounts are excreted in feces. About 75% of an oral dose is excreted in urine within 24 hr; about 43% is excreted unchanged and about 22% is excreted as pemoline conjugates.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

pemoline 从胃肠道吸收，血药浓度在 2-4 小时内达到峰值。成年人的多次给药研究表明，血清浓度在大约 3 天内达到平台期。在一项涉及成年人的研究中，单次口服 pemoline 的中枢神经系统兴奋作用相对较长，在 4 小时内达到峰值，持续至少 8 小时。然而，当 pemoline 用于治疗注意力缺陷障碍的儿童时，该药物的疗效逐渐显现，可能需要治疗 2 到 3 周后才能显现出治疗效果。

Pemoline is absorbed from the GI tract, and peak serum concentrations are achieved within 2-4 hours. Multiple-dose studies in adults indicate that serum concentrations plateau in about 3 days. In a study involving adults, the CNS stimulant effect of a single oral dose of pemoline was relatively long, reaching its peak within 4 hr and lasting at least 8 hr. However, when pemoline is administered to children in the treatment of attention deficit disorder, the drug has a gradual onset of action and therapeutic effects may not be apparent until 2 or 3 weeks of therapy.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

由苯甲醛经过与氯仿缩合、水解得到α-羟基苯乙酸，再经酯化、环合而得匹莫林。

用途简介

匹莫林是一种中枢兴奋药，主要用于治疗小儿多动症。

反应信息

• 作为反应物：
  描述：

  匹莫林 在 三乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 1-benzoyl-4-(4-oxo-5-phenyl-4,5-dihydro-oxazol-2-yl)-piperazine
  参考文献：
  名称：

  抗疟药。1-（4-甲氧基肉桂酰基）-4-（5-苯基-4-氧代-2-恶唑啉-2-基）哌嗪及其衍生物的合成和抗疟活性。

  摘要：

  描述了1-（4-甲氧基肉桂酰基）-4-（5-苯基-4-氧代-2-恶唑啉-2-基）哌嗪的衍生物的制备及其对伯氏疟原虫的活性。通过1-（5-苯基-4-氧代-2-恶唑啉-2-基）哌嗪的酰化或烷基化来完成肉桂酰基的取代。5-苯基的修饰可以通过一系列涉及扁桃酸酯-二氢萘-哌嗪-哌莫啉的反应或通过5-芳基-2-硫-2,4-恶唑烷二酮与哌嗪或N-取代的哌嗪的反应来制备。以类似的方式，使匹莫林与N-芳基哌嗪，六氢-1H-1,4-二氮杂和2,6-二甲基哌嗪反应，以提供N-芳基哌嗪匹莫林衍生物和哌嗪部分的变异。制备了几种化合物，其中2-恶唑啉-4-酮环被其他杂环取代，以及几种开链类似物。发现有五个化合物（其中三个被5-苯基对位取代）和两个N-芳基哌嗪哌莫林衍生物对柏氏疟原虫有活性。剩余的活性化合物具有肉桂酰基的变化和5-苯基的取代。

  DOI：

  10.1021/jm00246a009
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 生成 匹莫林
  参考文献：
  名称：

  Aspelund, Acta Academiae Aboensis, Series B: Mathematica et Physica, 1939, vol. 12, # 5, p. 23

  摘要：

  DOI：

文献信息

• [EN] CYCLIC PHOSPHATE COMPOUNDS<br/>[FR] COMPOSÉS DE PHOSPHATE CYCLIQUE
  申请人：LIGAND PHARM INC

  公开号：WO2020219464A1

  公开（公告）日：2020-10-29

  Provided herein are cyclic phosphate compounds, their preparation and their uses, such as treating liver diseases or conditions or a disease or condition in which the physiological or pathogenic pathways involve the liver.

  本文提供了环磷酸酯化合物，它们的制备以及它们的用途，例如用于治疗肝脏疾病或病况，或者涉及肝脏的生理或病理途径的疾病或病况。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• Methods for treating cognitive/attention deficit disorders using tetrahydroindolone analogues and derivatives
  申请人：——

  公开号：US20030022892A1

  公开（公告）日：2003-01-30

  Methods for treating cognitive/attention deficit disorders in general using tetrahydroindolone derivatives and analogues, particularly tetrahydroindolone derivatives or analogues in which the tetrahydroindolone derivative or analogue is covalently linked to another moiety to form a bifunctional conjugate are disclosed. More specifically, methods and compositions for treating attention deficit disorder and attention deficit hyperactivity disorders in adults and children as well as mild cognitive impairment and dementia are provided. The compounds used to treat and/or palliate cognitive/attention deficit disorders in general include a tetrahydroindolone derivative or analogue comprises a 9-atom bicyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y 1 )-D, where Y 1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption or blood-brain barrier penetration of the derivative or analogue. The moiety A has a six-membered ring fused to a five-membered ring. The moiety A can have one, two, or three nitrogen atoms in the five membered ring. The moiety A can be a tetrahydroindolone moiety. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

  一般使用四氢吲哚酮衍生物和类似物治疗认知/注意力缺陷障碍的方法，特别是揭示了将四氢吲哚酮衍生物或类似物与另一物质共价连接以形成双功能共轭物的方法。更具体地，提供了用于治疗成人和儿童的注意力缺陷障碍和注意力缺陷多动障碍以及轻度认知障碍和痴呆症的方法和组合物。一般用于治疗和/或缓解认知/注意力缺陷障碍的化合物包括一个四氢吲哚酮衍生物或类似物，其包括一个9原子的双环物质A，通过连接物L连接到一个物质B，其中B是一个羧酸，一个羧酸酯，或者结构N(Y1)-D的物质，其中Y1可以是各种取代基之一，包括氢或烷基，D是增强药理效应、促进衍生物或类似物吸收或血脑屏障穿透的物质。物质A具有与一个五元环融合的六元环。物质A的五元环中可以有一个、两个或三个氮原子。物质A可以是四氢吲哚酮物质。物质B可以是各种物质之一，包括具有智力活性或其他生物或生理活性的物质。
• [EN] MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] MODULATEURS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES

  公开号：WO2017193063A1

  公开（公告）日：2017-11-09

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾患和症状的化合物、组合物和方法。
• Azabicyclic compounds for the treatment of disease
  申请人：——

  公开号：US20030232853A1

  公开（公告）日：2003-12-18

  The invention provides compounds of Formula I: 1 wherein Azabicyclo is 2 These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful in pharmaceuticals in which &agr;7 is known to be involved.

  这项发明提供了Formula I的化合物： 其中Azabicyclo是 这些化合物可以是药用盐或组合物的形式，可以是纯对映体形式或混合物，对已知涉及α7的药物具有用处。

表征谱图