舒宁 | 604-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 舒宁
• 中文别名: 去甲羟安定；羟苯二氮唑；7-氯-2,3-二氢-3-羟基-5-苯基-1H-1,4-苯并二氮杂卓-2-酮；奥沙西泮；7-氯-2,3-二氢-3-羟基-5-苯基-1,4(2H)-苯并二氮杂卓-2-酮；去甲羟基安定
• 英文名称: oxazepam
• 英文别名: 7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 604-75-1
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: ADIMAYPTOBDMTL-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：

  性质与稳定性：

  在常温常压下，该物质不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

奥沙西泮有一个主要的无活性代谢物，即葡萄糖醛酸苷结合物。S-异构体的葡萄糖醛酸化由UGT2B15催化。R-异构体的葡萄糖醛酸化由UGT2B7和UGT1A9催化。

Oxazepam has a single major inactive metabolite, a glucuronide conjugate. The glucuronidation of the S-isomer is catalyzed by UGT2B15. The glucuronidation of the R-isomer is catalyzed by UGT2B7 and UGT1A9.

来源:DrugBank

代谢

在给小鼠静脉注射氯拉卓后2小时内，跟踪了氯拉卓的代谢和抗惊厥效果。药物在1分钟时的ED50为12 mg/kg，对抗戊四唑诱导的惊厥（45 mg/kg静脉注射），在1小时时达到最低（2.0 mg/kg），在2小时时上升到2.7 mg/kg。在给予相应的ED50后，测定了血浆和大脑中未改变的氯拉卓及其代谢物，去甲基地西泮和奥沙西泮的浓度。在第一小时内可以在血浆中检测到未改变的氯拉卓，但从未在大脑中检测到，因此它可以被认为是无活性的前药。在给予氯拉卓相应的ED50后，1分钟和15分钟时大脑中去甲基地西泮和奥沙西泮的浓度显著高于更长的时间间隔。这可以用达到并绑定到苯二氮卓受体的时间滞后来解释。

The metabolism and the anticonvulsant effect of clorazepate were followed for 2 h after its i.v. administration to mice. The ED50 of the drug was 12 mg/kg at 1 min against pentetrazole-induced convulsions (45 mg/kg i.v.), it reached a minimum at 1 hr (2.0 mg/kg) and rose to 2.7 mg/kg at 2 h. The concentrations of unchanged clorazepate and its metabolites, desmethyldiazepam and oxazepam, were determined in plasma and brain after administration of the respective ED50s. Unchanged clorazepate could be detected in plasma for the first hour but never in brain, so it can be considered as inactive pro-drug. The brain concentrations of desmethyldiazepam and oxazepam after the respective ED50s of clorazepate were considerably higher at 1 and 15 min than after longer time intervals. This may be explained by a time lag needed to reach and bind to the benzodiazepine receptor.

来源:Hazardous Substances Data Bank (HSDB)

代谢

奥沙西泮通过直接与葡萄糖醛酸结合进行代谢。

... Oxazepam ... /is/ metabolized by direct conjugation with glucuronic acid.

来源:Hazardous Substances Data Bank (HSDB)

代谢

奥沙西泮是一种常用的1,4-苯二氮䓬类抗焦虑药物，在人体内以多态性代谢。然而，目前这种现象的分子基础尚不清楚。我们之前已经表明，S-奥沙西泮葡萄糖苷酸是奥沙西泮的主要代谢物，由UDP-葡萄糖苷酸转移酶（UGT）2B15选择性形成，而次要的R-奥沙西泮葡萄糖苷酸是由除UGT2B15之外的多个UGT产生的。使用来自同一组54个人肝的微体和DNA进行了表型-基因型研究。UGT2B15基因的测序揭示了三个非同义多态性，D85Y、T352I和K523T，变异等位基因频率分别为0.56、0.02和0.40。D85Y基因型对S-奥沙西泮葡萄糖苷酸化有显著影响（p = 0.012），85Y/Y肝中的中位活性（49 pmol/min/mg蛋白）低于85D/D肝（131 pmol/min/mg），而85D/Y肝的活性居中（65 pmol/min/mg）。在两个352T/I肝（135和210 pmol/min/mg）与剩余352T/T肝（中位数，64 pmol/min/mg）相比，S-奥沙西泮活性也有显著趋势（p = 0.049）升高。相反，K523T基因型对奥沙西泮葡萄糖苷酸化没有明显影响（p > 0.05）。供体性别也显著影响S-奥沙西泮葡萄糖苷酸化，男性（65 pmol/min/mg）与女性（39 pmol/min/mg）肝的中位活性有显著差异（p = 0.042）。R-奥沙西泮葡萄糖苷酸化不受基因型或性别的影响（p > 0.05）。总之，性别和D85Y基因型被确定为人类肝S-奥沙西泮葡萄糖苷酸化的主要决定因素，可能部分解释了人类受试者奥沙西泮葡萄糖苷酸化的多态性。

Oxazepam is a commonly used 1,4-benzodiazepine anxiolytic drug that is polymorphically metabolized in humans. However, the molecular basis for this phenomenon is currently unknown. We have previously shown that S-oxazepam glucuronide, the major oxazepam metabolite, is selectively formed by UDP-glucuronosyltransferase (UGT) 2B15, whereas the minor Roxazepam glucuronide is produced by multiple UGTs other than UGT2B15. Phenotype-genotype studies were conducted using microsomes and DNA prepared from the same set of 54 human livers. Sequencing of the UGT2B15 gene revealed three nonsynonymous polymorphisms, D85Y, T352I, and K523T, with variant allele frequencies of 0.56, 0.02, and 0.40, respectively. D85Y genotype showed a significant effect (p = 0.012) on S-oxazepam glucuronidation with lower median activities in 85Y/Y livers (49 pmol/min/mg protein) compared with 85D/D livers (131 pmol/min/mg), whereas 85D/Y livers were intermediate in activity (65 pmol/min/mg). There was also a significant trend (p = 0.049) for higher S-oxazepam activities in the two 352T/I livers (135 and 210 pmol/min/mg) compared with the remaining 352T/T livers (median, 64 pmol/min/mg). Conversely, K523T genotype had no apparent effect on oxazepam glucuronidation (p > 0.05). Donor gender also significantly influenced S-oxazepam glucuronidation with higher median activities in male (65 pmol/min/mg) compared with female (39 pmol/min/ mg) livers (p = 0.042). R-Oxazepam glucuronidation was not affected by either genotype or gender (p > 0.05). In conclusion, gender and D85Y genotype are identified as major determinants of S-oxazepam glucuronidation by human liver and may explain in part polymorphic oxazepam glucuronidation by human subjects.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在小鼠和 rats（以及人类）中，oxazepam 的代谢主要有三条途径：直接结合、苯环氧化和 diazepine 环收缩。在小鼠中，结合主要是与葡萄糖醛酸，主要随尿液排出；在大鼠中，结合主要是与硫酸，几乎全部随粪便排出。在酸性介质中不稳定的硫酸结合物可能是粪便中 oxazepam 的来源，但在小鼠中尚未检测到。使用循环灌注的雄性瑞士（CD-1）小鼠肝脏制剂的研究表明，在小鼠这个物种中，oxazepam 葡萄糖苷酸是主要的肝脏代谢物。oxazepam 也可以通过兔子的胎盘与葡萄糖苷酸结合，这与人类器官的情况相反。在大鼠中，苯环氧化比在小鼠（或人类）中更重要，二氢二醇（可能是 3',4'-二氢二醇，因为 2'-羟基衍生物尚未被发现）占 Fischer 344 大鼠 72 小时尿代谢物的约 30%。这种代谢物可能通过 arene 氧化物中间体形成，且在小鼠中未被发现，这对 oxazepam 的毒理学特性具有影响。在大鼠中，环收缩至 6-氯-4-苯基-2(1H)-喹唑啉羧酸的程度约为小鼠中观察到的程度的一半。

There are three major pathways of oxazepam metabolism in mice and rats (as in humans): direct conjugation, phenyl ring oxidation and diazepine ring contraction. In mice, conjugation is mainly with glucuronide, predominantly excreted in the urine; in rats, conjugation is mainly with sulfate, which is almost entirely eliminated in the feces. The sulfate conjugate of oxazepam, which is unstable in acidic media, may be the source of the fecal oxazepam It has not been detected in mice. Studies with recirculating, perfused male Swiss (CD-1) mouse liver preparations showed that oxazepam glucuronides are the dominant liver metabolites in this species. Oxazepam can also be conjugated with glucuronide by the placenta of rabbits, apparently in contrast to the human organ. Phenyl ring oxidation is more important in rats than in mice (or humans) and a dihydrodiol (probably the 3',4'- dihydrodiol, since 2'-hydroxy derivatives are not known) accounts for about 30% of the 72-hr urinary metabolites in Fischer 344 rats. This metabolite, which probably forms via an arene oxide intermediate and has not been found in mice, holds implications for the toxicological properties of oxazepam. In rats, ring contraction to 6-chloro-4-phenyl- 2(1H)-quinazoline carboxylic acid occurs to roughly one half of the extent seen in mice.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

与其他苯二氮卓类药物相似，奥沙西泮通过增强γ-氨基丁酸（GABA）在GABA-A受体上的作用，通过协同作用机制发挥其抗焦虑效果。GABA受体是离子otropic氯离子通道受体，产生抑制性突触后电位。当GABA激活时，GABA受体/氯离子通道复合物发生构象变化，允许氯离子通过通道。苯二氮卓类药物被认为通过增加GABA在其受体上的效果来发挥其作用。苯二氮卓类药物结合在GABA存在时通过增加通道开启的频率来增加氯离子电导。相比之下，巴比妥类药物通过延长通道保持开启的时间来增加GABA存在时的氯离子电导。GABA受体亚单位有18种亚型。认为α2β3γ2受体复合物的α2亚单位介导抗焦虑效果，而α1β2γ2受体复合物的α1亚单位介导镇静、抗惊厥和顺行性遗忘作用。

Similar to other benzodiazepines, oxazepam exerts its anxiolytic effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA-A receptors through a cooperative mechanism of action. GABA receptors are ionotropic chloride-linked channel receptors that produce inhibitory postsynaptic potentials. When activated by GABA, the GABA receptor/chloride ionophore complex undergoes a conformational change that allows the passage of chloride ions through the channel. Benzodiazepines are believed to exert their effect by increasing the effect of GABA at its receptor. Benzodiazepine binding increases chloride conductance in the presence of GABA by increasing the frequency at which the channel opens. In contrast, barbiturates increase chloride conductance in the presence of GABA by prolonging the time in which the channel remains open. There are 18 subtypes of the GABA receptor subunits. The α₂ subunit of the α₂β₃γ₂ receptor complex is thought to mediate anxiolytic effects while the α₁ subunit of the α₁β₂γ₂ receptor complex is thought to mediate sedative, anticonvulsant and anterograde amnesia effects.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

奥沙西泮与其他苯二氮䓬类药物一样，很少与血清ALT或碱性磷酸酶升高有关，临床上明显的奥沙西泮引起的肝损伤极为罕见，甚至可能根本不会发生。尽管奥沙西泮问世已有50多年，但尚未有关于其引起有症状的急性肝损伤的病例报告。尽管如此，奥沙西泮的产品标签中提到了肝功能失调和黄疸的可能性。已经报道了其他苯二氮䓬类药物，包括阿普唑仑、氯氮卓、氯硝西泮、地西泮、氟硝西泮、劳拉西泮和三唑仑，出现临床上明显的肝损伤的孤立单一病例。苯二氮䓬类药物引起的急性肝损伤的临床模式通常是胆汁淤积性的，严重程度从中度到中度，潜伏期为1到6个月。发热和皮疹不常见，自身抗体的形成也不常见。

Oxazepam, like other benzodiazepines, is rarely associated with serum ALT or alkaline phosphatase elevations, and clinically apparent liver injury from oxazepam is extremely rare, if it occurs at all. Despite its availability for more than 50 years, there have been no case reports of symptomatic, acute liver injury from oxazepam. Nevertheless, the possibility of liver dysfunction and jaundice are mentioned in the product label for oxazepam. Isolated single cases of clinically apparent liver injury have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, lorazepam, and triazolam. The clinical pattern of acute liver injury from benzodiazepines is typically cholestatic and mild-to-moderate in severity with a latency of 1 to 6 months. Fever and rash are uncommon as is autoantibody formation.

来源:LiverTox

毒理性

• 药物性肝损伤

化合物的名称:奥沙西泮

Compound:oxazepam

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：模糊的 DILI 关注

DILI Annotation:Ambiguous 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：5

Severity Grade:5

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

口服给药后，平均血浆峰浓度（Cmax）为450 mg/mL，大约在给药后3小时（Tmax）出现。

Following oral administration, peak plasma levels (Cmax) averaged 450 mg/mL and occurred approximately 3 hours (Tmax) after dosing.

来源:DrugBank

吸收、分配和排泄

• 消除途径

奥沙西泮主要通过尿液以葡萄糖醛酸代谢物的形式排出，粪便中大约含有21%的未改变药物。口服摄入的奥沙西泮的大部分在48小时内被排出体外。

Oxazepam is primarily eliminated in the urine as its glucuronide metabolite, with the feces containing approximately 21% of the unchanged drug. The majority of an orally ingested dose of oxazepam is excreted within 48 hours.

来源:DrugBank

吸收、分配和排泄

微小型猪（像人类一样）主要将奥沙西泮以葡萄糖苷酸形式排出，而在大鼠中则以芳香羟基化为主。在大鼠中，单次口服剂量为20 mg/kg bw的70.7 +/- 6.0%通过胆汁分泌后随粪便排出，而18.9 +/- 2.4%的剂量在尿液中找到。在给予CD-1小鼠口服剂量为22 mg/kg bw奥沙西泮的情况下，五天内从粪便中回收了57.8%，从尿液中回收了27.3%。...在胃灌注奥沙西泮之前，通过饮食给予2500 mg/kg饮食（ppm）奥沙西泮14天，导致小鼠从粪便转变为尿液排泄，但大鼠则没有，使得尿液排泄几乎增加了一倍。

The miniature swine (like humans) eliminated oxazepam primarily as the glucuronides, while aromatic hydroxylation predominated in the rat. In rats, 70.7 +/- 6.0% of a single oral dose of 20 mg/kg bw was eliminated in feces following biliary secretion, while 18.9 +/- 2.4% of the dose was found in the urine. In CD-1 mice given an oral dose of 22 mg/kg bw oxazepam, 57.8% was recovered from the feces and 27.3% was recovered from urine over five days. ... Treatment with 2500 mg/kg diet (ppm) oxazepam in the diet for 14 days before administration of oxazepam by gastric instillation led to a shift from fecal to urinary excretion in mice, but not rats, so that the urinary excretion almost doubled.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

奥沙西泮在脂肪组织中积累。发现给予小鼠5毫克/千克体重静脉注射的药物在脂肪组织/血液中的比率从1.7（在5分钟时）变化到4.9（在30分钟时）。药物在大脑中也有积累。小鼠大脑中奥沙西泮的最大浓度为14.3 +/- 0.17微克/克，大鼠为4.5 +/- 0.03微克/克，豚鼠为3.5 +/- 0.47微克/克，这些都是在5分钟时的数据。这些物种的大脑/血液药物水平比率从小鼠的1.1（在1分钟时）变化到11.3（在10小时时），大鼠从1.9（在1分钟时）变化到6.2（在1小时时），豚鼠从1.9（在5分钟时）变化到8.9（在5小时时）。

Oxazepam accumulates in adipose tissue. /It was/ found that adipose tissue/blood ratios of the drug in mice given 5 mg/kg bw intravenously varied from 1.7 (at 5 min) to 4.9 (at 30 min). Accumulation also occurred in the brain. Maximal concentrations of oxazepam in the brain were 14.3 +/- 0.17 ug/g in mice, 4.5 +/- 0.03 ug/g in rats and 3.5 +/- 0.47 ug/g in guinea-pigs, all at 5 min. Brain/blood drug level ratios in these species varied from 1.1 (at 1 min) to 11.3 (at 10 hr) in mice, from 1.9 (at 1 min) to 6.2 (at 1 hr) in rats and from 1.9 (at 5 min) to 8.9 (at 5 hr) in guinea-pigs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

30毫克奥沙西泮的最大吸收时间在18名男性中为2.2小时（范围，0.75-4.25小时），在20名女性中为3.1小时（范围，0.5-8.0小时）。在这项研究中，男性的最大血浆浓度为622 +/- 37 ng/mL，女性的为837 +/- 51 ng/mL。

/It was/ found that the time of maximum absorption of 30 mg oxazepam was 2.2 hr (range, 0.75-4.25 hr) in 18 men and 3.1 hr (range, 0.5-8.0 hr) in 20 women. The maximal plasma concentrations in this study were 622 +/- 37 ng/mL in men and 837 +/- 51 ng/mL in women.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

具有镇静、催眠、抗焦虑、抗癫痫及肌肉松弛作用。

用途简介

该物质具有以下作用：

• 镇静
• 催眠
• 抗焦虑
• 抗癫痫
• 肌肉松弛

反应信息

• 作为反应物：
  描述：

  舒宁 在 丙酮酸 作用下， 反应 7.0h， 以11.8 g的产率得到6-氯-4-苯基 喹唑啉-2-甲醛
  参考文献：
  名称：

  一种奥沙西泮杂质Ⅱ的制备工艺

  摘要：

  本发明提出了一种奥沙西泮杂质II的制备工艺，该工艺是以奥沙西泮为原料，在偶极溶剂中，加入催化剂丙酮酸，进行保温反应，反应完毕后经后处理得到奥沙西泮杂质II。本发明方法以奥沙西泮为原料，反应和后处理工艺简单，不需要使用液相制备柱技术进行分离纯化，可大幅缩短制备周期、降低制备成本、大幅提高杂质II的制备效率。该制备工艺具有原料易得，工艺过程简单，制备得到的奥沙西泮杂质II纯度较高等优点，可用于奥沙西泮生产中杂质的定性和定量分析，从而提高奥沙西泮的质量标准，为安全用药提供重要的指导意义。

  公开号：

  CN111777563A
• 作为产物：
  描述：

  去甲西泮 在 potassium tert-butylate 、 N-(sulfonyl)oxaziridine 作用下， 以 四氢呋喃 为溶剂， 以94.5 %的产率得到舒宁
  参考文献：
  名称：

  一种奥沙西泮的制备方法

  摘要：

  本发明属于物化学制备领域，公开了一种奥沙西泮的制备方法。本申请公开的奥沙西泮制备工艺，在不改变起始物料的情况下，通过三步反应，总收率可达70％，反应在温和条件下进行，减少了能源消耗，降低成本；合成路线短，后处理方便，减少了环境污染，使得本发明更符合低毒，低污染的绿色合成要求。

  公开号：

  CN114989102A
• 作为试剂：
  描述：

  腺苷 在 calf intestinal mucosa adenosine deaminase type IV 、 舒宁 作用下， 反应 0.05h， 生成 肌苷
  参考文献：
  名称：

  与奥沙西m和劳拉西m相互作用时腺苷脱氨酶的动力学和构象研究。

  摘要：

  奥沙西m和劳拉西m对腺苷脱氨酶（ADA）的抑制作用不同。在劳拉西m的情况下，温度升高引起抑制作用的增加，而更高的温度则降低奥沙西m的抑制作用；提出了劳拉西m相对于奥沙西m引起的整体结构变化。

  DOI：

  10.2174/092986610790226076

文献信息

• [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，老年性痴呆和与帕金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。
• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] IMIDAZOLIUM REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF D'IMIDAZOLIUM POUR SPECTROMÉTRIE DE MASSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021234004A1

  公开（公告）日：2021-11-25

  The present invention relates to compounds which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said compounds.

  本发明涉及适用于质谱的化合物，以及利用该化合物进行分析物分子的质谱测定方法。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。

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