氯米帕明 | 303-49-1

• 物质功能分类: 原料药 - 神经系统用药 - 抗抑郁、躁狂药
• 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: 氯米帕明
• 中文别名: N,N-二甲基-10,11-二氢-3-氯-5H-二苯并[b,f]氮杂卓-5-丙胺；氯丙咪嗪；安拿芬尼；海地芬；氯丙帕明
• 英文名称: Clomipramine
• 英文别名: chlomipramine；3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine；3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine
• CAS: 303-49-1
• 化学式: C₁₉H₂₃ClN₂
• mdl: MFCD00242755
• 分子量: 314.858
• InChiKey: GDLIGKIOYRNHDA-UHFFFAOYSA-N

物化性质

• 熔点：
  189.5°C
• 沸点：
  bp0.3 160-170°
• 密度：
  1.0568 (rough estimate)
• 溶解度：
  在水中的溶解度25 mg/mL
• 物理描述：
  Solid
• 蒸汽压力：
  4.07X10-7 mm Hg at 25 °C (est)
• 解离常数：
  pKa = 8.98 (amine) (est)
• 碰撞截面：
  174.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2397;2397;2415;2454;2419;2406;2430.1;2457;2405;2406;2448.5;2423.2

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

在肝脏中广泛代谢。主要活性代谢物是去甲基氯米帕明，它是通过CYP2C19、3A4和1A2酶将氯米帕明进行N-脱甲基化形成的。还会产生其他代谢物及其葡萄糖醛酸苷结合物。氯米帕明的其他代谢物包括通过8-羟基化形成的8-羟基氯米帕明，通过2-羟基化形成的2-羟基氯米帕明，以及通过N-氧化形成的氯米帕明N-氧化物。去甲基氯米帕明进一步代谢为通过8-羟基化形成的8-羟基去甲基氯米帕明和通过N-脱甲基化形成的二去甲基氯米帕明。8-羟基氯米帕明和8-羟基去甲基氯米帕明具有药理活性；然而，它们在临床上的相关性尚不清楚。

Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by <i>N</i>-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine <i>N</i>-oxide formed by <i>N</i>-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and <i>N</i>-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical relevance remains unknown.

来源:DrugBank

代谢

氯米帕明确切的代谢途径尚未完全阐明。氯米帕明似乎被广泛代谢为去甲基氯米帕明和其他代谢物以及它们的葡萄糖苷酸结合物。去甲基氯米帕明是主要的代谢物，由氯米帕明的N-去甲基化形成。氯米帕明的其他代谢物包括8-羟基氯米帕明、2-羟基氯米帕明和氯米帕明N-氧化物，它们似乎是通过8-羟基化、2-羟基化和N-氧化分别形成的。去甲基氯米帕明的代谢物包括8-羟基去甲基氯米帕明和二去甲基氯米帕明，它们显然是通过8-羟基化和N-去甲基化分别形成的。尽管去甲基氯米帕明具有药理活性，但它在治疗强迫症方面的疗效尚不清楚。8-羟基氯米帕明和8-羟基去甲基氯米帕明也具有药理活性，但它们存在的临床重要性仍然未知。

The exact metabolic fate of clomipramine has not been fully elucidated. Clomipramine appears to be extensively metabolized to desmethylclomipramine and other metabolites and their glucuronide conjugates. Desmethylclomipramine, the principal metabolite, is formed by N-demethylation of clomipramine. Other metabolites of clomipramine include 8-hydroxyclomipramine, 2-hydroxyclomipramine, and clomipramine N-oxide, which appear to be formed via 8-hydroxylation, 2-hydroxylation, and N-oxidation, respectively. The metabolites of desmethylclomipramine include 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which apparently are formed via 8-hydroxylation and N-demethylation, respectively. Although desmethylclomipramine is pharmacologically active, its efficacy in obsessive-compulsive disorder is not known. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine also are pharmacologically active but the clinical importance of their presence remains unknown.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯米帕明和去甲基氯米帕明的羟基化似乎受到遗传控制（类似于脱布里奎和司巴丁）。在对脱布里奎羟基化进行表型鉴定的健康成年人中，广泛代谢者与不良代谢者在去甲基氯米帕明羟基化的程度方面是可以区分的。在一部分患者中，去甲基氯米帕明的血药浓度高于预期，这些患者后来被发现是不良代谢者。有限的数据表明，CYP2D6，一种涉及司巴丁/脱布里奎氧化多态性的细胞色素P-450同工酶，参与了氯米帕明和去甲基氯米帕明的8-羟基化以及氯米帕明的2-羟基化。此外，氯米帕明的去甲基化可能涉及CYP2C，后者涉及S-美芬妥因氧化多态性，以及CYP1A2。

The hydroxylation of clomipramine and desmethylclomipramine appears to be under genetic control (similar to that of debrisoquine and sparteine). In healthy adults who were phenotyped for debrisoquine hydroxylation, extensive metabolizers were distinguishable from poor metabolizers with regard to the extent of hydroxylation of desmethylclomipramine. Blood concentrations of desmethylclomipramine were higher than expected in a limited number of patients who subsequently were found to be poor metabolizers. Limited data suggest that CYP2D6, a cytochrome P-450 isoenzyme implicated in the sparteine/debrisoquine oxidation polymorphism, is involved in the 8-hydroxylation of clomipramine and desmethylclomipramine and in the 2-hydroxylation of clomipramine. In addition, demethylation of clomipramine may involve CYP2C, which is implicated in the S-mephenytoin oxidation polymorphism, and CYP1A2.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯米帕明（CMI）及其主要去甲基代谢物去甲基氯米帕明（DCMI）在两种瑞士小鼠（NMRI和CD1）腹腔注射后的命运进行了研究。对其在各种组织中的分布进行研究，结果显示在肺、肾周脂肪和肾脏中的固定最为明显，而在大脑中则只有中等程度的固定。两种分子的药代动力学参数在脑组织和血浆中进行了确定。吸收迅速（CMI的tmax=14分钟），代谢迅速（DCMI的tmax=17或18分钟，视品种而定），并且从血浆和脑组织中迅速消除。前两个阶段在两个品系中相似，但CMI从NMRI小鼠的血浆和脑中消除更快（血浆t1/2=53分钟，而CD1小鼠为165分钟）。这两个值都远低于人类的报告值（平均血浆t1/2=24小时）...

The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 hr). ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯米帕明已知的人类代谢物包括2-羟基氯米帕明、10-羟基氯米帕明、N-去甲基氯米帕明和8-羟基氯米帕明。

Clomipramine has known human metabolites that include 2-hydroxy-clomipramine, 10-hydroxy-clomipramine, N-Desmethylclomipramine, and 8-hydroxy-clomipramine.

来源:NORMAN Suspect List Exchange

毒理性

• 毒性总结

氯米帕明是一种强效的、但并非完全选择性的5-羟色胺再摄取抑制剂（SRI），因为其主要活性代谢物去甲氯米帕明主要作为去甲肾上腺素再摄取的抑制剂。已经注意到α1-受体阻滞和β-下调，这很可能是氯米帕明短期效应的作用机制。像其他三环类药物一样，钠通道和NMDA受体的阻断可能是氯米帕明在治疗慢性疼痛，特别是神经性疼痛中的作用机制。

Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. &alpha;₁-receptor blockage and &beta;-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

肝脏测试异常在接受三环类抗抑郁药治疗的病人中据报道最高可达16%，但升高通常不会超过正常上限的3倍。在接受氯米帕明治疗的病人中，血清转氨酶升高的情况在1%到3%的病人中出现，这些异常通常是轻微的、无症状的并且是暂时的，即使在继续用药的情况下也会逆转。与许多三环类抗抑郁药一样，接受氯米帕明治疗的病人中也有极少数出现临床上明显的急性肝损伤的案例。氯米帕明引起的药物性肝病的临床特征尚未被很好地定义。由三环类抗抑郁药引起的急性肝损伤通常在开始用药后1到4周内出现，表现为乏力，随后出现深色尿和黄疸。已经描述了肝细胞损伤和胆汁淤积性损伤模式。这种损伤通常为轻到中度严重，当停用三环类药物时恢复迅速。免疫过敏特征如皮疹、发热和嗜酸性粒细胞增多并不常见，通常检测不到自身抗体。致命的病例极为罕见。

Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. Serum aminotransferase elevations during clomipramine therapy are reported in 1% to 3% of patients and the abnormalities were usually mild, asymptomatic and transient, reversing even with continuation of medication. As with many tricyclic antidepressants, rare instances of clinically apparent acute liver injury have been reported in patients taking clomipramine. The clinical features of cases of drug induced liver disease from clomipramine have not been well defined. The acute liver injury caused by tricyclic antidepressants typically arises within 1 to 4 weeks of starting the medication and presents with fatigue followed by dark urine and jaundice. Both hepatocellular and cholestatic patterns of injury have been described. The injury is usually mild-to-moderate in severity and recovery is rapid when the tricyclic is discontinued. Immunoallergic features such as rash, fever and eosinophilia are not common and autoantibodies are generally not detected. Fatal cases are extremely rare.

来源:LiverTox

毒理性

• 药物性肝损伤

化合物：氯米帕明

Compound:clomipramine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：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

严重等级：8

Severity Grade:8

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

从胃肠道吸收良好，口服给药后。口服的生物利用度大约为50%，这是由于首次通过肝脏代谢广泛。食物不影响生物利用度。单次口服50毫克剂量后，血浆浓度峰值出现在2-6小时。血浆浓度峰值范围从56 ng/mL到154 mg/mL（平均，92 ng/mL）。不同个体之间的血浆浓度存在较大差异，部分原因是由于遗传差异导致的氯米帕明代谢不同。平均而言，在多次口服给药后1-2周达到稳态血浆浓度。吸烟似乎会降低氯米帕明的稳态血浆浓度，但不会降低其活性代谢物去甲氯米帕明。

Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occurred 2-6 hours following oral administration of a single 50 mg dose. The peak plasma concentration ranged from 56 ng/mL to 154 mg/mL (mean, 92 ng/mL). There are large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.

来源:DrugBank

吸收、分配和排泄

• 消除途径

尿液（51-60%）和通过胆汁消除的粪便（24-32%）

Urine (51-60%) and feces via biliary elimination (24-32%)

来源:DrugBank

吸收、分配和排泄

• 分布容积

~ 17 L/kg（范围：9-25 L/kg）。氯米帕明能够分布到脑脊液、大脑以及进入母乳中。

~ 17 L/kg (range: 9-25 L/kg). Clomipramine is capable of distributing into the cerebrospinal fluid, the brain, and into breast milk.

来源:DrugBank

吸收、分配和排泄

盐酸氯米帕明口服给药后似乎能很好地从胃肠道吸收。然而，广泛的首过代谢将其口服生物利用度降低到大约50%。据报道，盐酸氯米帕明口服胶囊和溶液的生物等效。食物似乎不会显著影响从胶囊中吸收盐酸氯米帕明的生物利用度。

Clomipramine hydrochloride appears to be well absorbed from the GI tract following oral administration. However, extensive first-pass metabolism decreases its oral bioavailability to about 50%. The oral capsules and solution of clomipramine hydrochloride reportedly are bioequivalent. Food does not appear to substantially affect the bioavailability of clomipramine from the capsules.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一个病例报告中，测量了一名婴儿的血浆氯米帕明浓度，其母亲在怀孕期间每天接受125毫克氯米帕明氢氯化物。...产后第一周后，将母亲氯米帕明氢氯化物的剂量增加到每天150毫克，氯米帕明在乳汁中的浓度在稳态时为血浆氯米帕明浓度的80-160%。

In one case report, plasma clomipramine concentrations were measured in an infant whose mother was receiving clomipramine hydrochloride 125 mg daily during pregnancy. ... After the first week postpartum, the mother's dosage of clomipramine hydrochloride was increased to 150 mg daily and the concentration of clomipramine in milk was 80-160% of the concurrent plasma clomipramine concentration at steady state. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• RTECS号：
  HN9055000
• 海关编码：
  2933990090
• 储存条件：
  库房应保持通风、低温和干燥，并将存货与食品原料分开存放。

制备方法与用途

理化性质

氯米帕明是一种安全可靠、起效迅速的三环类抗抑郁药，常温下为白色或微黄色结晶性粉末；无臭，味苦；遇光颜色渐变黄。在冰醋酸或氯仿中极易溶解，在水或乙醇中易溶，在丙酮中微溶，在乙醚中几乎不溶。

适应症

氯米帕明可用于治疗各种抑郁状态、强迫性神经症和恐怖性神经症。

作用机制

氯米帕明通过抑制突触前膜对去甲肾上腺素（NA）与5-羟色胺（5-HT）的再摄取产生抗抑郁作用，同时具有抗焦虑与镇静效果。其抑制5-羟色胺再摄取的作用强于其他三环类药物，而抑制去甲肾上腺素再摄取则较弱，其抗胆碱能作用中等，镇静作用较低。口服吸收良好，治疗血药浓度为200～500ng/ml，1～2周可达稳态血浓度。经肝脏代谢，活性代谢产物去甲氯米帕明的浓度是原药的两倍。血浆蛋白结合率为96～97%，半衰期为21～31小时。约70%自尿排出，30%自粪便排出。适用于治疗内源性、反应性、神经性、隐匿性抑郁症以及各种抑郁状态；伴有抑郁症的精神分裂症；强迫症、恐怖症；多种疼痛等。此外，该药还能降低脑脊液和血小板中的5-羟基吲哚乙酸（5HIAA）水平，与治疗强迫症有关。它对D2受体、α肾上腺素受体及组胺受体有亲和力，并具有较强的抗胆碱能作用以及轻度拮抗多巴胺的作用。

用法与用量

成人常用量：

1. 治疗抑郁症，一次25mg，一日3次。成人门诊限量为一日250mg，住院限量每日300mg。
2. 治疗强迫症，开始一日25mg，一日1次。前两周逐渐增加至每日100mg，数周后可再增加，但每日不超过250mg。
3. 老年人开始一日20-30mg，根据需要和耐受情况缓慢增加用量，每日不超过75mg为宜。
4. 小儿每日10mg，连续服药10天后，5～7岁儿童增至20mg，8～14岁增至20～25mg，14岁以上增至50mg或按需要量分次服用。

药物相互作用

（1）与乙醇并用可增强中枢神经抑制作用。 （2）与抗惊厥药并用会降低其疗效，需调整用量。 （3）与抗组胺药或抗胆碱药并用，药效相互加强，需及时调整用量。 （4）胍乙啶与氯米帕明合用会使前者的降压作用减弱。但用量不超过每日150mg时，不会影响其疗效。 （5）与雌激素或含雌激素的避孕药并用会增加不良反应，并降低抗抑郁效能。 （6）与单胺氧化酶抑制剂合用可产生高血压危象，且已有死亡报道。一般应在前者停用两周后使用。 （7）与肾上腺素受体激动药并用可能导致严重高血压和高热。 （8）与甲状腺制剂合用会互相增效导致心律失常，两者均需减量。

不良反应

常见口干、出汗、眩晕、震颤、视力模糊、排尿困难、体位性低血压。偶见皮肤过敏、粒细胞减少。大剂量给药出现焦虑、心律不齐、传导阻滞、失眠等。罕见肝损伤、发热和癫痫发作。

用途

用作抗抑郁症药。

类别与特性

类别：有毒物质
毒性分级：高毒
急性毒性：

• 口服-大鼠 LD50: 613 毫克/公斤
• 口服-小鼠 LD50: 380 毫克/公斤

可燃性危险特性：热分解排出有毒氮氧化物和氯化物烟雾。
储运特性：

• 库房应通风低温干燥。
• 与食品原料分开存放。

灭火剂：水、二氧化碳、泡沫、干粉。

反应信息

• 作为反应物：
  描述：

  氯米帕明 在 盐酸 、 2,4,5,6-四(9H-咔唑-9-基)异酞腈 、 重水 、 lithium carbonate 、 三异丙基硅烷硫醇 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 以80%的产率得到
  参考文献：
  名称：

  用于光氧化还原氘的A啶催化剂的可扩展合成

  摘要：

  抽象的 光催化方法的不断发展激发了有机催化剂的设计，以补充常用和珍贵的聚吡啶基过渡金属体系。本文描述了合适的suitable啶染料的可扩展合成及其在光氧化还原氘中的应用。以克为单位制备的cri啶鎓催化剂可以在温和条件下以高收率和选择性对药学相关的支架进行氘化。 光催化方法的不断发展激发了有机催化剂的设计，以补充常用和珍贵的聚吡啶基过渡金属体系。本文描述了合适的suitable啶染料的可扩展合成及其在光氧化还原氘中的应用。以克为单位制备的cri啶鎓催化剂可以在温和条件下以高收率和选择性对药学相关的支架进行氘化。

  DOI：

  10.1055/s-0039-1690694
• 作为产物：
  描述：

  2-溴苯胺 在 甲醇 、 palladium diacetate 、 caesium carbonate 、 magnesium 、 三苯基膦 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 71.5h， 生成 氯米帕明
  参考文献：
  名称：

  增强芳基溴化物的反应性和选择性：二苯并[b，f]氮杂环庚烷衍生物的一种补充方法

  摘要：

  二氢二苯并[ b，f ]氮杂和二苯并[ b，f ]氮杂可以通过钯催化从芳基溴化物，邻溴代苯胺和降冰片烯或降冰片二烯有效合成。该协议可以访问二苯并[ b，f]氮杂core核在两个芳环上均包含多个吸电子取代基，并补充了先前报道的方法，在该方法中优先使用富含电子的芳基碘化物。KI的存在，即使是低于化学计量的量，对于该三组分反应也至关重要。适当添加碘化物阴离子对反应速率和选择性具有显着影响。的三环类抗抑郁药氯米帕明（安那芬尼正式三步合成®）也被描述。

  DOI：

  10.1002/cctc.201800940

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。
• NAPHTHALENE-BASED INHIBITORS OF ANTI-APOPTOTIC PROTEINS
  申请人：Pellecchia Maurizio

  公开号：US20090105319A1

  公开（公告）日：2009-04-23

  Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently selected from the group consisting of H, C(O)X, C(O)NHX, NH(CO)X, SO 2 NHX, and NHSO 2 X, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, and a heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

  使用阿波戈司宝及其衍生物治疗炎症的方法被披露。此外，还描述了一组具有结构A的化合物，或其药学上可接受的盐、水合物、N-氧化物或溶剂化合物： 其中每个R独立地选自H、C(O)X、C(O)NHX、NH(CO)X、SO2NHX和NHSO2X组成的组，其中X选自烷基、取代烷基、芳基、取代芳基、烷基芳基和杂环的组。A组化合物可用于治疗各种疾病或疾病，如癌症。
• [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。

表征谱图