米赛林 | 24219-97-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 米赛林
• 中文别名: 米安色林；米安舍林
• 英文名称: mianserin
• 英文别名: mianserine；2-methyl-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine；Bolvidon；5-methyl-2,5-diazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(19),8,10,12,15,17-hexaene
• CAS: 24219-97-4
• 化学式: C₁₈H₂₀N₂
• 分子量: 264.37
• InChiKey: UEQUQVLFIPOEMF-UHFFFAOYSA-N

物化性质

• 沸点：
  397.6°C (rough estimate)
• 密度：
  1.0092 (rough estimate)
• 溶解度：
  溶于二甲基亚砜
• 物理描述：
  Solid
• 碰撞截面：
  164.5 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2207;2198.8;2208

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

米安色林在女性人类、兔子和大鼠中的代谢被研究。在女性人类中，未改变的米安色林、8-羟基米安色林和米安色林-2-氧化物在尿液中被发现并鉴定。这两种代谢物占总尿液放射性的60%以上；结合型和未结合型的米安色林大约占35%。在兔子中，米安色林主要代谢为8-羟基米安色林和一种未识别的8-羟基米安色林的酯；大约只有2.4%的米安色林未改变。少量的2-甲酰基去甲基米安色林被分离出来。在大鼠中，主要的代谢物是8-羟基去甲基米安色林。大鼠将米安色林主要代谢为8-羟基化合物，在一定程度上还会代谢为去甲基化的代谢物。作者们得出结论，米安色林主要通过三种主要途径进行代谢：8-羟基化、去甲基化和2-氧化物的形成。/盐酸米安色林/

Mianserin metabolism was studied in female humans, rabbits, and rats. ... In human females, unchanged mianserin, 8-hydroxymianserin and mianserin-2-oxide were isolated and identified in urine. The two metabolites were over 60 percent of the total urinary radioactivity; conjugated and unconjugated mianserin accounted for approximately 35 percent. In rabbits, mianserin was metabolized largely as 8-hydroxymianserin and an unidentified ester of 8-hydroxymianserin; only about 2.4 percent was unchanged mianserin. Small amounts of 2-formyldesmethylmianserin were isolated. The principal metabolite in rats was 8-hydroxydesmethylmianserin. Rats metabolized mianserin principally to 8-hydroxy compounds and to a lesser extent to demethylated metabolites. The authors conclude that mianserin is metabolized by three main pathways: 8-hydroxylation, demethylation, and 2-oxide formation. /Mianserin HCl/

来源:Hazardous Substances Data Bank (HSDB)

代谢

为了测量米安色林及其主要活性代谢物去甲米安色林的稳态血浆浓度，并分析各种临床因素对这些血浆浓度的影响，我们在76名20至70岁的抑郁症患者中测量了米安色林和去甲米安色林的稳态血浆浓度，这些患者每晚睡前服用30毫克/天的米安色林，持续3周，如有需要，剂量可增至60毫克/天。这些化合物的稳态血浆浓度在个体间有相当大的差异；只有43%的患者的米安色林加去甲米安色林的血浆浓度在治疗范围内。随着年龄的增长，米安色林的血浆浓度显著增加，而米安色林加去甲米安色林的血浆浓度保持不变。性别、吸烟和合用苯二氮卓类药物并不影响药物的代谢。没有证据表明这些化合物的动力学随着剂量的增加而呈非线性。

To measure steady-state plasma concentrations of mianserin and its major active metabolite, desmethylmianserin, and to analyze the effects of various clinical factors on these plasma concentrations, steady-state plasma concentrations of mianserin and desmethylmianserin were measured in 76 depressed patients, ages 20-70 yr, receiving 30 mg/day mianserin at bedtime for 3 wk with doses increased up to 60 mg/day if needed. There were considerable interindividual variations in the steady-state plasma concentrations of these compounds; the plasma concentrations of mianserin plus desmethylmianserin were within the therapeutic range in only 43% of the patients. With advancing age, the plasma concentrations of mianserin increased significantly, while those of mianserin plus desmethylmianserin remained unchanged. Sex, smoking, and coadministration of benzodiazepines did not affect the drug's metabolism. There was no evidence that the kinetics of these compounds were nonlinear with increasing doses.

来源:Hazardous Substances Data Bank (HSDB)

代谢

米安色林已知的人类代谢物包括8-羟基米安色林、去甲基米安色林和米安色林N-氧化物。

Mianserine has known human metabolites that include 8-Hydroxymianserin, Desmethylmianserin, and Mianserin N-oxide.

来源:NORMAN Suspect List Exchange

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：米安色林未获得美国食品药品监督管理局在美国的上市批准，但在其他国家可用。有限的信息表明，母亲每日剂量高达60毫克时，在乳汁中产生的水平较低，预计不会对哺乳的婴儿造成任何不良影响，特别是如果婴儿已超过2个月大。在更多数据可用之前，米安色林在哺乳期间应谨慎使用并密切监测。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发表信息。 ◉ 对泌乳和母乳的影响：一项观察性研究调查了在怀孕前两年内服用抗抑郁药的2859名妇女的结果。与怀孕期间未服用抗抑郁药的妇女相比，整个孕期（三个季度）都服用抗抑郁药的妇女在出院时哺乳的可能性降低了37%。仅在第三季度服用抗抑郁药的妇女在出院时哺乳的可能性降低了75%。仅在第一季度和第二季度服用抗抑郁药的妇女在出院时哺乳的可能性没有降低。研究中未具体说明母亲使用的抗抑郁药种类。 一项回顾性队列研究比较了2001年至2008年的医院电子医疗记录，研究对象是晚期妊娠期间被开出抗抑郁药的妇女（n = 575）、患有精神疾病但未接受抗抑郁药治疗的妇女（n = 1552）以及没有精神疾病诊断的妇女（n = 30,535）。服用抗抑郁药的妇女在出院时哺乳的可能性比没有精神疾病诊断的妇女低37%，但与未接受治疗的精神疾病母亲相比，哺乳的可能性没有降低。这些母亲中没有人在服用米安色林。 在一项涉及1999年至2008年的80,882对挪威母婴对的研究中，有392名妇女报告在产后新开始使用抗抑郁药，有201名妇女报告她们从怀孕期间继续使用抗抑郁药。与未暴露的对照组相比，晚期妊娠使用抗抑郁药与哺乳开始的几率降低7%有关，但对哺乳持续时间或专一性没有影响。与未暴露的对照组相比，新开始或重新开始使用抗抑郁药与6个月时主要哺乳几率降低63%和任何哺乳几率降低51%有关，以及突然停止哺乳的风险增加2.6倍。具体抗抑郁药未提及。

◉ Summary of Use during Lactation:Mianserin is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal doses up to 60 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Until more data are available, mianserin should be used with careful monitoring during breastfeeding. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified. A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking mianserin. In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

未结合和总（未结合加结合）米安色林、去甲基米安色林和8-羟基米安色林对映体的浓度在12名患者中，在引入卡马西平之前和之后进行了测量。米安色林的剂量为60毫克/天，卡马西平共同给药400毫克/天，持续4周，并在引入卡马西平后每周间隔取血样。每周，卡马西平显著降低了未结合和总（S）-米安色林（效力更强的对映体）以及未结合和总（R）-米安色林的血浆浓度。平均而言，未结合和总（S）-米安色林以及未结合和总（R）-米安色林的血浆浓度分别为引入卡马西平前的相应值的55%，56%，66%和55%。这些结果强烈表明，卡马西平诱导的主要CYP酶CYP3A4参与了米安色林两种对映体的代谢。未结合和总（S）-8-羟基米安色林的浓度也显著降低（平均而言，浓度为引入卡马西平前相应值的69%）。相反，卡马西平仅轻微改变了未结合和总（S）-去甲基米安色林、（R）-去甲基米安色林和（R）-8-羟基米安色林的血浆浓度。从临床角度来看，由于最近提出了（S）-米安色林的治疗窗口，如果引入400毫克/天的卡马西平作为联合用药，那么对于一个已经将（S）-米安色林浓度稳定在此治疗窗口内的患者，其消旋米安色林的剂量需要大约加倍。

Concentrations of the enantiomers of unconjugated and of total (unconjugated plus conjugated) mianserin, desmethylmianserin and 8-hydroxymianserin were measured in 12 patients before and after the introduction of carbamazepine. The dose of mianserin was 60 mg/d, carbamazepine was coadministered at 400 mg/d for 4 weeks, and blood samples were taken at weekly intervals after the introduction of carbamazepine. Each week, carbamazepine significantly decreased plasma concentrations of unconjugated and total (S)-mianserin (the more potent enantiomer) and of unconjugated and total (R)-mianserin. On average, plasma concentrations of unconjugated and total (S)-mianserin and of unconjugated and total (R)-mianserin were 55%, 56%, 66%, and 55%, respectively, of the corresponding values before introduction of carbamazepine. These results strongly suggest the involvement of CYP3A4, the major CYP enzyme induced by carbamazepine, in the metabolism of both enantiomers of mianserin. A strong decrease in the concentrations of (S)-8-hydroxymianserin was also measured (on average, the concentrations were 69% of the corresponding values before carbamazepine introduction). Conversely, plasma concentrations of unconjugated and of total (S)-desmethylmianserin, (R)-desmethylmianserin, and (R)-8-hydroxymianserin were only slightly modified by carbamazepine. From a clinical point of view, as a therapeutic window for (S)-mianserin has been recently suggested, the dose of racemic mianserin for a patient whose (S)-mianserin concentrations have been stabilized within this therapeutic window would need to be approximately doubled if carbamazepine, at 400 mg/d, is introduced as a comedication.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究评估了米安色林与中枢作用抗高血压药物之间的相互作用，研究对象包括正常志愿者和接受可乐定或甲基多巴治疗的原发性高血压患者。给正常志愿者首次服用20毫克米安色林后，出现了显著的镇静效果和短暂性的体位性低血压。在正常志愿者中，预先使用米安色林对单次口服300微克可乐定的血压反应没有影响。然而，可乐定单独引起的缓慢性心率降低被显著减弱。在患者研究中，无论是首次服用30毫克米安色林后，还是在连续使用米安色林一周或两周后，都没有观察到血压控制方面的显著变化。这些研究没有证据表明，添加米安色林治疗会导致可乐定或甲基多巴的抗高血压效果出现临床上显著的损害。

The interaction between mianserin and centrally-acting antihypertensive drugs was evaluated in normal volunteers and in patients with essential hypertension receiving either clonidine or methyldopa. The administration of the first dose of 20 mg mianserin to the normal volunteers was associated with a significant sedative effect and transient postural hypotension. In the normal volunteers, the blood pressure responses to a single oral dose of 300 ug clonidine were not modified by pretreatment with mianserin. The bradycardia associated with clonidine alone, however, was significantly attenuated. In the patient study, no significant changes in blood pressure control were observed, either after the first dose of 30 mg mianserin or after one and two weeks' continued treatment with mianserin. There is no evidence from these studies that the addition of mianserin therapy results in a clinically significant impairment of the antihypertensive effects of clonidine or methyldopa.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，并在需要时辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预期癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用生理盐水连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。 ... 开始静脉输液，使用D5W/SRP：“保持开放”，最低流量/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

经口服吸收。

Absorbed following oral administration.

来源:DrugBank

吸收、分配和排泄

进行了一项盐酸米安色林（mianserin HCl）的药代动力学研究，研究对象为六名健康男性。在这些受试者不同时间接受了以下治疗：静脉恒速输注5毫克盐酸米安色林，持续1小时；口服单次剂量60毫克，分为两片，每片30毫克；以及口服溶液60毫克。各治疗之间的洗脱期为1个月。在给药后的120小时内，按照预定时间采集血液样本。测定了血浆样本中的米安色林浓度，并对结果进行了药代动力学分析。静脉数据可以通过一个三室模型充分描述，而口服数据则通过一个两室模型描述，两者都具有一阶转移和消除速率常数。米安色林的平均血浆清除率为19 +/- 2 L/小时（平均值 +/- 标准误），动力学生分布容积为444 +/- 250 L，稳态分布容积为242 +/- 171 L，消除半衰期为33 +/- 5小时。按照吸收程度计算的绝对生物利用度，溶液为22 +/- 3%，片剂为20 +/- 3%。溶液的平均峰值浓度为79 +/- 11纳克/毫升，片剂为54 +/- 5纳克/毫升；溶液的平均达峰时间为1.1 +/- 0.2小时，片剂为1.4 +/- 0.2小时。溶液的平均吸收半衰期为0.43 +/- 0.13小时，片剂为0.39 +/- 0.11小时。

A pharmacokinetic study with mianserin HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin HCl in 1 hr, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 hr following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 L/hr (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 L, the steady-state volume of distribution 242 +/- 171 L and the elimination half-life 33 +/- 5 hr. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng/mL and for the tablets 54 +/- 5 ng /mL; mean peak time for the solution was 1.1 +/- 0.2 hr and for the tablets 1.4 +/- 0.2 hr. The mean absorption half-life for the solution was 0.43 +/- 0.13 hr and for the tablets 0.39 +/- 0.11 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

我们研究了8名患有抑郁症的住院患者在单次（60毫克）剂量米安色林后的药代动力学。血浆水平在患者之间存在相当大的变异性。平均峰血浆浓度（±SEM）为114 ± 26 ng/ml，在1到3小时之间达到。米安色林在血浆中的下降是双相的。平均消除半衰期为21.6 ± 3.1小时，范围从10.7到40.8小时。估计的首过损失从26%到48%（平均37%），低于三环类抗抑郁药三级胺的报告。平均表观分布体积（15.7 ± 2.2 L/kg；9.7到28.8 L/kg）与丙咪嗪相当，但略低于马普替林。表观总清除率从0.33到0.81 L/hr/kg（平均±SEM，0.52 ± 0.05 L/hr/kg），与马普替林相当。我们的结果表明，米安色林的药代动力学在大多数方面与三级胺三环类抗抑郁药（例如，丙咪嗪）和四环类的马普替林相似。

We studied mianserin kinetics after a single (60 mg) dose in eight inpatients suffering from depression. There was a considerable interpatient variability in plasma levels. Mean peak plasma levels (+/- SEM) were 114 +/- 26 ng/ml and were reached between 1 and 3 hr. The decline of mianserin levels in plasma was biphasic. The mean elimination t 1/2 was 21.6 +/- 3.1 hr and ranged from 10.7 to 40.8 hr. The estimated first-pass loss ranged from 26% to 48% (mean, 37%) and was lower than that reported for tertiary amine tricyclic antidepressants. The mean apparent volume of distribution (15.7 +/- 2.2 L/kg; 9.7 to 28.8 L/kg) was in the range of that for imipramine but somewhat lower than for maprotiline. Apparent total body clearance ranged from 0.33 to 0.81 L/hr/kg (mean +/- SEM, 0.52 +/- 0.05 L/hr/kg) and was of the order of that after maprotiline. Our results indicate that mianserin kinetics are in most respects similar to those of tertiary amine tricyclic antidepressants (e.g., imipramine) and the tetracyclic maprotiline.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品运输编号：
  UN 3249
• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 储存条件：
  2-8℃

制备方法与用途

生物活性方面，Mianserin是一种H1受体反向激动剂。

反应信息

• 作为反应物：
  描述：

  米赛林 在 氘氧化钠 、 重水 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 20.0h， 生成 <10,10-(2)H2>mianserin
  参考文献：
  名称：

  氘代棉桃素的合成及NMR分析

  摘要：

  已经合成了11种棉桃素的氘代类似物，并通过1 H和13 C NMR进行了分析。基于这些化合物，可以解释棉兰素1 H光谱中的芳族部分。

  DOI：

  10.1002/recl.19831021007
• 作为产物：
  描述：

  3,4-dioxomianserin 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.5h， 以64%的产率得到米赛林
  参考文献：
  名称：

  Hulinska, Hana; Polivka, Zdenek; Jilek, Jiri, Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 8, p. 1820 - 1844

  摘要：

  DOI：

文献信息

• [EN] ARYL SULFONAMIDE AMINE COMPOUNDS AND THEIR USE AS 5-HT6 LIGANDS<br/>[FR] COMPOSÉS AMINES D'ARYLSULFONAMIDE ET LEUR UTILISATION EN TANT QUE LIGANDS DE 5-HT6
  申请人：SUVEN LIFE SCIENCES LTD

  公开号：WO2010032258A1

  公开（公告）日：2010-03-25

  The present invention relates to novel aryl sulfonamide amine compounds of the formula (I), their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates described herein and pharmaceutically acceptable compositions containing them.

  本发明涉及新颖的芳基磺酰胺胺化合物的化学式（I），其互变异构体，其立体异构体，其多晶形式，本文所述的药用可接受盐，所述的药用可接受溶剂化合物和含有它们的药用可接受组合物。
• ARYL SULFONAMIDE AMINE COMPOUNDS AND THEIR USE AS 5-HT6 LIGANDS
  申请人：Nirogi Ramakrishna

  公开号：US20120129816A1

  公开（公告）日：2012-05-24

  The present invention relates to novel aryl sulfonamide amine compounds of the formula (I), their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates described herein and pharmaceutically acceptable compositions containing them.

  本发明涉及新颖的芳基磺酰胺胺化合物的公式（I），其互变异构体，其立体异构体，其多晶形式，其在此处描述的药用可接受盐，其在此处描述的药用可接受溶剂化合物以及含有它们的药用可接受组合物。
• Imidazole and benzimidazole derivatives useful as histamine H3 antagonists
  申请人：Aslanian G. Robert

  公开号：US20060166960A1

  公开（公告）日：2006-07-27

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: n is 2-5; R is R 3 -aryl, R 3 -heteroaryl, R 3 -cycloalkyl, R 3 -heterocycloalkyl, alkyl, haloalkyl, —OR 4 , —SR 4 or —S(O) 1-2 R 5 ; R 1 and R 2 are H or optionally substituted phenyl or optionally substituted and X is —O— or —S—; or R 1 and R 2 , together with the carbon atoms to which they are attached form optionally substituted and X is —O—, —S— or —NR 7 —; Z is and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I; also disclosed are methods of treating allergy, allergy-induced airway responses, congestion, obesity and metabolic syndrome using the compounds of Formula I, as well as combinations with other drugs useful for treating those diseases.

  揭示了以下公式化合物或其药学上可接受的盐或溶剂，其中：n为2-5；R为R3-芳基，R3-杂环芳基，R3-环烷基，R3-杂环烷基，烷基，卤代烷基，—OR4，—SR4或—S(O)1-2R5；R1和R2为H或可选择地取代的苯基或可选择地取代的，X为—O—或—S—；或R1和R2，连同它们连接的碳原子形成可选择地取代的，X为—O—，—S—或—NR7—；Z为，其余变量如规范中所定义；还揭示了包括公式I化合物的药物组合物；还揭示了使用公式I化合物治疗过敏、过敏引起的气道反应、充血、肥胖和代谢综合征的方法，以及与其他用于治疗这些疾病的药物的组合。
• [EN] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES AS HISTAMINE H3 ANTAGONISTS<br/>[FR] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR H3 DE L'HISTAMINE
  申请人：SCHERING CORP

  公开号：WO2003103669A1

  公开（公告）日：2003-12-18

  Disclosed are histamine H3 antagonists of the formula (I) wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula (I) in combination with a H1 receptor antagonist.

  揭示了公式（I）中的组胺H3拮抗剂，其中R1是苯并咪唑酮衍生物，M1和M2是可选择地取代的碳或氮，R2包括可选择地取代的芳基或杂环基，其余变量如规范中所定义。还揭示了包括公式（I）化合物的药物组合物。还揭示了使用公式（I）化合物治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）的方法。还揭示了使用公式（I）化合物与H1受体拮抗剂结合治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）。
• [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。