麦角乙二胺 | 50-37-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 中文名称: 麦角乙二胺
• 中文别名: 麥角醯胺
• 英文名称: lysergide
• 英文别名: LSD；lysergic acid diethylamide；[3H]-LSD；[3H]-lysergic acid diethylamide；d-LSD；9,10-didehydro-N,N-diethyl-6-methylergoline-8β-carboxamide；(D)-lysergic acid diethylamide；lysergic acid diethylamine；(6aR,9R)-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
• CAS: 50-37-3
• 化学式: C₂₀H₂₅N₃O
• 分子量: 323.438
• InChiKey: VAYOSLLFUXYJDT-RDTXWAMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

三份病例报告被提出，包括尸检发现和毒理筛选结果，测试呈阳性的是强效的致幻药物麦角酸二乙基酰胺（LSD）。对大脑组织和股骨血液中的LSD及其主要代谢物进行了量化，并且在可获得的情况下，还量化了血肿和尿液中的LSD。根据之前发表的程序，使用液-液提取和超高效液相色谱-串联质谱（UHPLC-MS/MS）对生物样本中的LSD、其主要代谢物2-氧-3-羟基-LSD（氧代-HO-LSD）和异-LSD进行了量化。

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给13名受试者服用160微克的剂量后...在人类中，LSD在肝脏通过羟基化和葡萄糖醛酸苷结合被广泛转化为无活性代谢物。...尿液中发现的主要代谢物是2-羟基麦角酰胺。

Following a dose of 160 ug to 13 subjects ... in humans, LSD is extensively transformed in the liver by hydroxylation and glucuronide conjugation to inactive metabolites. ...A major metabolite found in urine is 2-oxylysergide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

这项研究提供了确凿的证据，表明O-H-LSD是在人肝微粒体和肝细胞与LSD孵育后产生的代谢产物。

The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠、豚鼠和恒河猴中，对(14)C-LSD的代谢和消除的定性和定量方面进行了研究。(...)(14)C-LSD几乎被这三种动物完全代谢，很少有未改变的药物被排出。已识别的代谢物包括13-和14-羟基-LSD及其葡萄糖醛酸苷、2-氧代-LSD、脱乙基LSD和一个萘基甲酸衍生物。然而，各种代谢物的性质和数量在不同物种之间存在重要的差异。在大鼠和豚鼠中，主要的代谢物是13-和14-羟基-LSD的葡萄糖醛酸苷，它们在尿液和胆汁中都有发现。豚鼠在尿液和胆汁中排出了大量的2-氧代-LSD。脱乙基LSD在这两种物种中都是次要的尿液代谢物。LSD的代谢在恒河猴中似乎更为复杂。尿液中至少含有九种代谢物，其中四种被鉴定如下：13-和14-羟基-LSD（作为葡萄糖醛酸苷）、脱乙基LSD和一个萘基甲酸衍生物。与大鼠和豚鼠不同，13-和14-羟基-LSD的葡萄糖醛酸苷只存在于少量中。在剩余的五种未鉴定代谢物中，有三种是主要的。已经研究了在大鼠中(14)C-异-LSD的胆汁代谢物，并显示它们与从(14)C-LSD产生的代谢物相似，即13-和14-羟基-异-LSD及其葡萄糖醛酸苷和2-氧代-异-LSD。

The qualitative and quantitative aspects of the metabolism and elimination of (14)C-LSD in the rat, guinea pig and rhesus monkey have been investigated. ...(14)C-LSD is almost completely metabolized by all three species and little unchanged drug is excreted. The metabolites identified were 13- and 14-hydroxy-LSD and their glucuronic acid conjugates, 2-oxo-LSD, de-ethyl LSD and a naphthostyril derivative. There occur, however, important species differences in the nature and amounts of the various metabolites. In the rat and guinea pig the major metabolites were the glucuronic acid conjugates of 13- and 14-hydroxy-LSD which were found in both urine and bile. The guinea pig excreted significant amounts of 2-oxo-LSD in urine and bile. De-ethyl LSD was a minor urinary metabolite in both species. The metabolism of LSD appeared to be more complicated in the rhesus monkey. The urine contained at least nine metabolites of which four were identified as follows: 13- and 14-hydroxy-LSD (as glucuronic acid conjugates) de-ethyl LSD and a naphthostyril derivative. Unlike the rat and guinea pig the glucuronic acid conjugates of 13- and 14-hydroxy-LSD were only present in small amounts. Of the remaining five unidentified metabolites, three were major. The biliary metabolites of (14)C-iso-LSD in the rat have been studied and been shown to be similar to those produced from (14)C-LSD, namely 13- and 14-hydroxy-iso-LSD and their glucuronic acid conjugates and 2-oxo-iso-LSD.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：LSD是一种无色、无味和无味的固体。它是一类受控物质。在生化研究中，它被用作血清素的拮抗剂。LSD曾作为实验性辅助药物用于研究和治疗精神障碍。人体研究：由于LSD的拟交感神经作用，它对心血管系统有显著影响。过量服用可能会导致心动过速、高血压、心律失常、休克和呼吸暂停。LSD的特征是联觉和“拖尾”。联觉是将一种感官模式转换为另一种，例如看到音乐的彩色振动，或者闻到紫色。拖尾是在物体移动时，紧随其后的正性残像。对LSD的不良反应很常见。急性LSD可能会导致“糟糕的旅行体验”。恐惧的想法会压倒用户，失去洞察力，认为这是一种药物体验；由此产生的急性恐慌反应通常需要去急诊室。急性躁狂、精神分裂症、抑郁和永久性精神病都是LSD滥用导致的，特别是在边缘稳定的人身上。耐受性会发生，但没有撤退状态。拟交感神经效应包括瞳孔扩张、潮红、震颤、反射亢进、高热、心动过速、血压升高、毛发直立、出汗和共济失调。可能会出现恶心和呕吐，严重中毒可能导致昏迷、癫痫和呼吸暂停。使用LSD后可能会发生神经阻滞恶性综合征。肌肉活检可能显示肌水肿、局部坏死和糖原和脂质耗竭。报告了四种慢性反应：(a)长期精神病反应，(b)抑郁和自杀意念，(c)闪回，(d)加重预先存在的精神病。从那时起，又描述了另一种诊断类别：致幻剂持续感知障碍（HPPD）。对140名承认在怀孕前或怀孕期间使用LSD的妇女及其配偶进行了148次怀孕的观察。有83名活产新生儿；8个有重大出生缺陷。有65个流产；53个治疗性和12个自发性。治疗性流产的14个胚胎中有4个显示明显异常。第一季度怀孕的43%以自发性流产告终。8次连续怀孕中有4次导致胚胎或婴儿缺陷。12名妇女中有8名在18个月内无法再次怀孕。只有在高剂量的LSD下，人类体细胞和染色体才会发生显著变化。动物研究：LSD在发育中的动物中长期给药可能会抑制身体生长，可能是通过改变生长激素的分泌，通过改变其神经内分泌控制。在11天的小鼠胚胎中，注射LSD后发现中枢神经系统异常，剂量为第7天的0.05至1.0微克。在大鼠中，通过口服或皮下注射（分别为20微克和5微克）在妊娠第1至第4天给药，导致胎儿丢失。没有报告特定的出生缺陷。在第8天给仓鼠使用0.08至410微克/千克的LSD，发现在12天胚胎中中枢神经系统缺陷的小幅增加。

IDENTIFICATION AND USE: LSD is a colorless, odorless and tasteless solid. It is a Schedule I controlled substance. It is used in biochemical research as antagonist to serotonin. LSD has been used experimentally as adjunct in study and treatment of mental disorders. HUMAN STUDIES: LSD has significant cardiovascular effects owing to its sympathomimetic actions. Tachycardia, hypertension, arrhythmias, shock, and respiratory arrest occur with severe overdose. Synesthesias and "trails" are characteristic of LSD. Synesthesias are a translation of one sensory modality into another, such as seeing colored vibrations of music, or smelling purple. Trails are formed positive afterimages that remain immediately behind an object as it moves across the subject's visual field. Adverse reactions to LSD are common. Acutely, LSD can produce a "bad trip." Frightening thoughts overwhelm the user, with a loss of insight that this is a drug experience; the resulting acute panic reaction generally necessitates a visit to the emergency department. Acute mania, schizophrenia, depression, and permanent psychoses have resulted from LSD abuse, particularly in someone of borderline stability. Tolerance occurs, but there is no withdrawal state. Sympathomimetic effects include mydriasis, flushing, tremor, hyperreflexia, hyperthermia, tachycardia, increased blood pressure, piloerection, diaphoresis, and ataxia. Nausea and vomiting may occur, and severe toxicity can result in coma, seizures, and respiratory arrest. Neuroleptic malignant syndrome may occur after LSD use. Muscle biopsy may show myoedema, focal necrosis, and glycogen and lipid depletion. Four chronic reactions were reported: (a) prolonged psychotic reactions, (b) depression and suicidal ideation, (c) flashbacks, and (d) exacerbation of preexisting psychiatric illness. Since then, another diagnostic category has been described: hallucinogen persisting perception disorder (HPPD). One hundred forty women and their consorts, admitting to the use of LSD prior to or during pregnancy were observed through 148 pregnancies. There were 83 live newborns; 8 had major congenital defects. There were 65 abortions; 53 therapeutic and 12 spontaneous. Four of 14 embryos from therapeutic abortions showed gross anomalies. Forty-three percent of first-trimester pregnancies ended in spontaneous abortions. Four of eight serial pregnancies resulted in defective embryos or infants. Eight of 12 women have been unable to conceive again over an 18-month period. Significant changes in human somatic cells and in chromosomes occurred only at high doses of LSD. ANIMAL STUDIES: LSD, when administered chronically to developing animals, can inhibit body growth probably by altering the secretion of growth hormone through modifications of its neuroendocrine control. Central nervous system abnormalities were reported in day 11 mouse embryos after injecting 0.05 to 1.0 ug of LSD on day 7. In rats, fetal loss was produced by administering LSD by mouth or sc (20 ug and 5 ug respectively) between the 1st and 4th day of gestation. No specific congenital defects were reported. Using LSD 0.08 to 410 ug/kg in the hamster on the 8th day, found a small increase in defects of the central nervous system in 12 day embryos.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

LSD优先通过在脑干中缝核、蓝斑和皮层作为5-HT1A受体的激动剂来抑制血清素能神经元的放电。它还在突触后的5-HT1A位点充当部分激动剂，并且对其他5-HT1亚型5-HT1B、5-HT1D和5-HT1E具有高亲和力。LSD的致幻效果是由于其能够在5-HT2A受体上充当部分激动剂，尤其是在新皮层的锥体细胞上。激活5-HT2A还会导致皮层谷氨酸水平的增加。LSD对5-HT2C、5-HT5A、5-HT6和5-HT7受体的作用也有描述，但它们的重要性尚不确定。此外，LSD在中央多巴胺D1和D2受体上表现出激动和拮抗的行为。

LSD preferentially inhibits serotonergic cell firing by acting as an agonist at the 5-HT1A receptors in the raphe nuclei, locus coeruleus, and cortex. It also acts as a partial agonist on the postsynaptic 5-HT1A site and has high affinity for the other 5-HT1 subtypes 5-HT1B, 5-HT1D, and 5-HT1E. LSD's hallucinogenic effects are caused by its ability to act as a partial agonist at the 5-HT2A receptor, especially on neocortical pyramidal cells. Activation of 5-HT2A also leads to increased cortical glutamate levels. Effects of LSD on 5-HT2C, 5-HT5A, 5-HT6, and 5-HT7 receptors have also been described, but their significance remains uncertain. In addition, LSD shows agonistic and antagonistic behavior at the central dopamine D1 and D2-receptors. (L1925, A2918)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

慢性LSD毒性效应包括闪回、精神疾病以及潜在精神障碍的加剧，特别是精神分裂症。过量使用可能导致“糟糕的旅行”，其特点是极度焦虑、好斗、混乱和恐慌发作。LSD被认为不具有成瘾性，且没有观察到撤药综合征。由于其相对较高的治疗指数，没有直接因单独使用LSD而导致的死亡案例。（A2915, L1925）

Chronic effects of LSD toxicity include flashbacks, psychosis, and exacerbation of latent mental disorders, particularly schizophrenia. Overdosage can result in “bad trips” that are characterized by intense anxiety, combativeness, confusion, and panic attacks. LSD is not considered to be addictive, and withdrawal syndrome are absent. Because of its relatively high therapeutic index, no deaths have been directly attributed to LSD use alone. (A2915, L1925)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

迅速吸收。口服（通常在吸水纸、方糖或明胶等基质上）(L1925)；肌肉注射或静脉注射(L1925)

Rapidly absorbed. Oral (usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin) (L1925); Intramuscular or intravenous injection (L1925)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

迅速吸收。

Rapidly absorbed.

来源:DrugBank

吸收、分配和排泄

/LSD/ 在肝脏通过羟基化和葡萄糖苷酸化代谢转化，并主要以药理上不活跃的化合物形式排出体外。

/LSD/ is converted metabolized in the liver via hydroxylation and glucuronidation, and excreted predominantly as a pharmacologically inactive compound.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服后，效果在大约30分钟内显现，并可能持续8到12小时或更长时间。药效的持续时间和强度取决于剂量。

When taken orally, the effects become apparent within about 30 minutes and may continue for 8 to 12 hours or more. The duration and intensity of effects are dose-dependent.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给13名受试者服用160微克的剂量后，血浆浓度变化很大，最高可达9微克/升。在24小时内，只有大约1%以不变的形式在尿液中排出。

Following a dose of 160 ug to 13 subjects, plasma concentrations varied considerably up to 9 ug/L. Only about 1 % is excreted unchanged in the urine in 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠、豚鼠和恒河猴中，对(14)C-LSD的代谢和消除的定性和定量方面进行了研究。注射(1毫克/千克)剂量的大鼠在96小时内通过粪便排出了73%的(14)C，通过尿液排出了16%，通过呼出的空气以(14)CO2的形式排出了3.4%。类似剂量处理的豚鼠在96小时内通过粪便排出了40%，通过尿液排出了28%，通过呼出的(14)CO2排出了18%。恒河猴(0.15毫克/千克肌肉注射)在96小时内通过尿液排出了39%的(14)C，通过粪便排出了23%。在大鼠和豚鼠中发生了大量的(14)C-LSD胆汁排泄。胆管插管的大鼠在5小时内通过胆汁排出了静脉注射剂量(1.33毫克/千克)的68%，豚鼠在6小时内排出了52%...

The qualitative and quantitative aspects of the metabolism and elimination of (14)C-LSD in the rat, guinea pig and rhesus monkey have been investigated. Rats given an i.p. dose (1 mg/kg) excreted 73% of the (14)C in the feces, 16% in the urine and 3.4% in the expired air as (14)CO2 in 96 hr. Guinea pigs similarly dosed, excreted 40% in the feces, 28% (urine) and 18% (expired (14)CO2) in 96 hr. Rhesus monkeys (0.15 mg/kg i.m.) eliminated 39% of the (14)C in the urine and 23% in the feces in 96 hr. Extensive biliary excretion of (14)C-LSD occurred in both the rat and guinea pig. Bile duct-cannulated rats excreted 68% of an i.v. dose (1.33 mg/kg) in the bile in 5 hr and the guinea pig 52% in 6 hr...

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  麦角乙二胺 在 potassium carbonate 、 锌 作用下， 以 四氯化碳 、 氯仿 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 154.0h， 生成 (6aR,9R)-7-Isopropyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid diethylamide
  参考文献：
  名称：

  Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives

  摘要：

  A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative.

  DOI：

  10.1021/jm00147a022
• 作为产物：
  描述：

  9,10-didehydro-N,N-diethyl-6-cyanoergoline-8β-carboxamide 在 sodium acetate 、 溶剂黄146 、 锌 作用下， 反应 5.5h， 生成 麦角乙二胺
  参考文献：
  名称：

  Stachulski, Andrew V.; Nichols, David E.; Scheinmann, Feodor, Journal of Chemical Research - Part S, 1996, # 1, p. 30 - 31

  摘要：

  DOI：
• 作为试剂：
  描述：

  、 2-溴麦角酸二乙基酰胺 在 四(三苯基膦)钯 dichloromethane N,N-dimethylformamide 、 四氢呋喃 、 麦角乙二胺 、 Chloroform;methanol;propan-2-one 、 tetrahydrofuran methanol 、 乙腈 、 水 、 甲醇 作用下， 以 N,N-二甲基甲酰胺 、 dichloromethane N,N-dimethylformamide 为溶剂， 反应 0.5h， 以to give a residue as crude [3H]-LSD (26.7 mCi, Radiochemical Purity ca. 90%)的产率得到麦角乙二胺
  参考文献：
  名称：

  Method for labeling with tritium

  摘要：

  本发明提供了一种氚标记方法，允许在制备的最后阶段引入氚，从而制备具有高比活度的氚标记化合物，以及由该方法制备的该化合物。

  公开号：

  US20050158240A1

文献信息

• [EN] DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERTO<br/>[FR] DERIVES DE DIARYL ET ARYLHETEROARYL UREE UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR DE LA SEROTONINE 5-HT2A UTILES POUR LA PROPHYLAXIE ET LE TRAITEMENT DE TROUBLES ASSOCIES A CE DERNIER
  申请人：ARENA PHARM INC

  公开号：WO2005012254A1

  公开（公告）日：2005-02-10

  The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

  本发明涉及某些Formula (I)的吡唑衍生物及其药物组合物，可调节5-HT2A 5-羟色胺受体的活性。该类化合物及其药物组合物用于预防或治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性缺血性发作、心绞痛、中风、心房颤动、减少血凝块形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、吉尔·德·拉·图雷特综合征、躁狂症、器质性或NOS精神病、精神病性障碍、精神病、急性精神分裂症、慢性精神分裂症、NOS精神分裂症及相关疾病、睡眠障碍、睡眠障碍、糖尿病相关疾病等的方法。本发明还涉及预防或治疗5-HT2A 5-羟色胺受体介导的疾病的方法，结合多巴胺D2受体拮抗剂如氟哌啶醇，分别或联合给药。
• [EN] COMPOUNDS USEFUL AS CSF1 MODULATORS<br/>[FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS DU FACTEUR 1 DE STIMULATION DE COLONIES
  申请人：REDX PHARMA PLC

  公开号：WO2016051193A1

  公开（公告）日：2016-04-07

  This invention relates to novel compounds and to pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as Colony Stimulating Factor 1 Receptor (cFMS) modulators (e.g. cFMS inhibitors). This invention also relates to processes for preparing the compounds, uses of the compounds in treatment and methods of treatment employing the compounds. Specifically, the invention relates to the use of the compounds for the treatment of cancer and autoimmune diseases.

  这项发明涉及新颖化合物以及包含这些新颖化合物的药物组合物。更具体地，该发明涉及用作集落刺激因子1受体（cFMS）调节剂（例如cFMS抑制剂）的化合物。这项发明还涉及制备这些化合物的方法，这些化合物在治疗中的用途以及利用这些化合物进行治疗的方法。具体而言，该发明涉及利用这些化合物治疗癌症和自身免疫性疾病。
• NOVEL SUBSTITUTED-1-H-QUINAZOLINE-2,4-DIONE DERIVATIVES, PREPARATION METHOD THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：Seong Churlmin

  公开号：US20090203708A1

  公开（公告）日：2009-08-13

  Disclosed herein are novel substituted-1H-quinazoline-2,4-dione derivatives, a preparation method thereof, and a pharmaceutical composition containing the same. The novel substituted-1H-quinazoline-2,4-dione derivatives are excellent in binding affinity and selectivity for 5-HT6 receptors over other receptors, inhibit serotonin(5-HT)-stimulated cAMP accumulation, and disrupt apomorphine(2 mg/kg, i.p.)-induced hyperactivity in rats. Thanks to these effects, the derivatives are useful in the treatment of 5-HT6 receptor-related central nervous system diseases.

  本文披露了一种新型的取代-1H-喹唑啉-2,4-二酮衍生物，其制备方法以及含有该衍生物的药物组合物。这种新型的取代-1H-喹唑啉-2,4-二酮衍生物在与其他受体相比对5-HT6受体的结合亲和力和选择性方面表现出色，抑制5-羟色胺（5-HT）刺激的cAMP积累，并破坏大鼠中阿波莫啡（2 mg/kg，i.p.）诱导的过度活动。由于这些效果，这些衍生物在治疗与5-HT6受体相关的中枢神经系统疾病中非常有用。
• 3-aryl--3-methyl-quinoline-2, 4-diones, preparation method thereof, and pharmaceutical composition containing the same
  申请人：Seong Churlmin

  公开号：US20060084676A1

  公开（公告）日：2006-04-20

  The present invention relates to compounds of 3-aryl-3-methyl-quinoline-2,4-diones acting as a 5HT6 receptor antagonist, a preparation method thereof, and a pharmaceutical composition containing the same for treatment of the central nervous system disorders. The compounds of 3-aryl-3-methyl-quinoline-2,4-diones according to the present invention may be valuably used for treatment of a 5HT6 receptor relating disorders because of its excellent binding affinity for the 5HT6 receptor and excellent selectivity for the 5HT6 receptor over other receptors.

  本发明涉及作为5HT6受体拮抗剂的3-芳基-3-甲基喹啉-2,4-二酮化合物，其制备方法以及含有该化合物的用于治疗中枢神经系统疾病的药物组合物。根据本发明的3-芳基-3-甲基喹啉-2,4-二酮化合物可用于治疗与5HT6受体相关的疾病，因为其对5HT6受体具有优异的结合亲和力，并且对5HT6受体具有优异的选择性，而且相对于其他受体具有优异的选择性。
• Robust Kalman filtering for continuous-time systems with norm-bounded nonlinear uncertainties
  作者：P. Shi、Y. Kaya

  DOI：10.1093/imamci/17.4.363

  日期：2000.12.1

  In this paper we study the problem of robust Kalman filtering for a class of uncertain linear continuous-time systems. The system under consideration is subjected to time-varying, norm-bounded, nonlinear parameter uncertainties in state and measurement equations. Stability of the above system is analyzed. A state estimator is designed such that the covariance of the estimation error is guaranteed to be within a certain bound for all admissible uncertainties, which is in terms of solutions of two algebraic Riccati equations.

  本文研究了一类不确定线性连续时间系统的稳健卡尔曼滤波问题。所考虑的系统在状态和测量方程中受到时变、范数有界的非线性参数不确定性的影响。对上述系统的稳定性进行了分析。设计了一种状态估计器，使得对于所有可容许的不确定性，估计误差的协方差保持在某个界限之内，这涉及到两个代数Riccati方程的解。