右芬氟拉明 | 3239-44-9

• 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: 右芬氟拉明
• 中文别名: 右旋芬氟那明
• 英文名称: dexfenfluramine
• 英文别名: (+)-fenfluramine；(S)-fenfluramine；dexfenflumarine；d-fenfluramine；fenfluramine；(2S)-N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine
• CAS: 3239-44-9
• 化学式: C₁₂H₁₆F₃N
• 分子量: 231.261
• InChiKey: DBGIVFWFUFKIQN-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

在大剂量使用dexfenfluramine的动物中，会导致血清素能标记物的减少，但迄今为止研究的所有物种都与人在动力学和代谢上没有足够的相似性，不能作为安全性研究的有效模型。因此，研究了dexfenfluramine及其活性代谢物dexnorfenfluramine在给予口服dexfenfluramine hydrochloride（2 mg/kg）的狒狒、恒河猴和食蟹猴中的血浆动力学，以探究这些灵长类动物中是否有人类生物分布的特别相似性。2. 该药物迅速N-去乙基化生成dexnorfenfluramine，在所有灵长类动物中达到相对较低的平均最大血浆浓度（Cmax）12-14 ng/ml，并且在此之后迅速消失，半衰期（t1/2）在狒狒和恒河猴中为2到3小时，在食蟹猴中为6小时。其正常代谢物达到更高的平均Cmax（52-97 ng/ml），半衰期更长，从恒河猴的大约11小时到食蟹猴的22小时不等。代谢物与母药的比例（14-37），以血浆曲线下面积（AUC）计算，远超过人类（< 1），高于迄今为止所有研究物种。3. 在猴子和人类中进行的比较重复剂量模拟表明，灵长类动物的剂量需要增加10倍才能达到可比的dexfenfluramine稳态血浆Cmax，产生的正常代谢物水平是人类的数倍，而为了达到可比的代谢物Cmax，母药的水平相应地会过低。4. 由于dexfenfluramine和dexnorfenfluramine在血清素能系统中的作用机制不同，因此这些灵长类动物都不是与人类相比接触活性物质的安全性评估的合适模型。

Large doses of dexfenfluramine in animals cause a decrease of serotoninergic markers but none of the species so far investigated shows sufficient kinetic and metabolic similarity with man to be a valid model for safety studies. The plasma kinetics of dexfenfluramine and its active metabolite dexnorfenfluramine were therefore studied in baboon, rhesus and cynomolgus monkeys given dexfenfluramine hydrochloride orally (2 mg/kg) in order to investigate whether any of these primates have a biodisposition particularly similar to man. 2. The drug was rapidly N-deethylated to dexnorfenfluramine achieving comparatively low mean maximum plasma levels (Cmax) of 12-14 ng/ml in all primates, and rapidly disappeared thereafter with half-lives (t1/2) ranging from 2 to 3 h in the baboon and rhesus monkey to 6 h in the cynomolgus monkey. Its normetabolite reached higher mean Cmax (52-97 ng/ml) and the t1/2's were longer, varying from about 11 h in the rhesus monkey to 22 h in the cynomolgus monkey. The metabolite-to-parent drug ratio (14-37), in terms of plasma area under curve (AUC), greatly exceeded that in man (< 1), being higher than in all species investigated so far. 3. Comparative repeat dose simulation in monkey and man indicated that the dosage in primates would need to be increased 10-fold to achieve comparable dexfenfluramine steady-state plasma Cmax, producing nor-metabolite levels several times those in man, whilst for comparable metabolite Cmax, those of the parent drug would be correspondingly too low. 4. In view of the different mechanism of action of dexfenfluramine and dexnorfenfluramine within the serotoninergic system none of these primates is therefore a suitable model for safety assessment in terms of exposure of the active moieties in comparison with man.

来源:Hazardous Substances Data Bank (HSDB)

代谢

dexfenfluramine作为食欲抑制剂被广泛用于治疗肥胖。最近的研究表明,与广泛代谢者相比,较差代谢者dexfenfluramine的明显非肾脏清除率显著降低,这表明多态性表达的酶CYP2D6参与了dexfenfluramine的代谢。在本研究中,使用人肝微粒体和酵母表达的重组酶来研究体外dexfenfluramine的代谢。在人肝微粒体中,dexfenfluramine的主要产物是nordexfenfluramine,还有少量新代谢物N-hydroxynordexfenfluramine,以及酮和醇衍生物的形成。在1-1000微摩尔底物浓度下,nordexfenfluramine形成的Eadie-Hofstee图(v对v/[s])在所检测的四个肝微粒体样本中有三个呈双相,高亲和力酶和低亲和力酶的平均Km值分别为3和569微摩尔。在约已知治疗血浆浓度(0.5微摩尔)的底物浓度下,磺胺唑和酮康唑对微粒体dexfenfluramine N-脱烷基几乎没有抑制作用,而奎尼丁在7个肝样本中可抑制33~100%,7,8-萘黄酮的抑制率为0~58%。在人肝微粒体中,dextromethorphan O-脱甲基化活性与dexfenfluramine(1微摩尔)N-脱烷基化活性之间也存在显著相关性(rs=0.79,n=10,P<0.01)。Dexfenfluramine是CYP2D6介导的dextromethorphan O-脱甲基化在人肝微粒体中的特异性抑制剂(IC50 46微摩尔),但未显著抑制人肝微粒体中CYP1A2、2A6、2C9、2C19、2E1和3A等其他细胞色素P450同种型的选择性活性。酵母表达的重组人CYP2D6以高亲和力(Km 1.6微摩尔,Vmax 0.18 nmol min(-1) nmol P450(-1))将dexfenfluramine代谢为nordexfenfluramine,这是唯一观察到的产物。重组CYP1A2是低亲和力酶(Km 301微摩尔,Vmax 1.12 nmol min(-1) nmol P450(-1)),并产生nordexfenfluramine和少量N-hydroxynordexfluramine。这是首次详细研究人肝微粒体和重组人P450体外代谢dexfenfluramine的研究。我们能够确定CYP2D6(高亲和力)和CYP1A2(低亲和力)是人肝微粒体中介导dexfenfluramine N-脱烷基的主要酶。

Dexfenfluramine has been widely used as an appetite suppressant in the treatment of obesity. It was recently shown that the apparent non-renal clearance of dexfenfluramine was significantly lower in poor metabolizers than in extensive metabolisers of debrisoquine which suggested the involvement of the polymorphically expressed enzyme, CYP2D6, in dexfenfluramine metabolism. In this study, human liver microsomes and yeast-expressed recombinant enzymes were used to examine dexfenfluramine metabolism in vitro. In human liver microsomes, the major product of dexfenfluramine was nordexfenfluramine with lesser amounts of a novel metabolite, N-hydroxynordexfenfluramine, and ketone and alcohol derivatives being formed. Eadie-Hofstee plots (v against v/[s]) of nordexfenfluramine formation between 1 and 1000 microM substrate concentration were biphasic in three of four liver microsome samples examined, with mean Km values of 3 and 569 microM for the high and low affinity enzymes, respectively. At a substrate concentration (0.5 microM) around the known therapeutic plasma concentration, there was negligible inhibition of microsomal dexfenfluramine N-dealkylation by sulphaphenazole and ketoconazole, but between 33 and 100% inhibition by quinidine, and 0-58% inhibition by 7,8-naphthoflavone in seven liver samples. In human liver microsomes, there was also a significant correlation (rs= 0.79, n = 10, P < 0.01) between dextromethorphan O-demethylation and dexfenfluramine (at 1 microM) N-dealkylation activities. Dexfenfluramine was a specific inhibitor (IC50 46 microM) of CYP2D6-mediated dextromethorphan O-demethylation in human liver microsomes but did not appreciably inhibit six other cytochrome P450 isoform-selective activities for CYP1A2, 2A6, 2C9, 2C19, 2E1 and 3A activities in human liver microsomes. Yeast-expressed recombinant human CYP2D6 metabolized dexfenfluramine with high affinity (Km 1.6 microM, Vmax 0.18 nmol min(-1) nmol P450(-1)) to nordexfenfluramine which was the sole product observed. Recombinant CYP1A2 was a lower affinity enzyme (Km 301 microM, Vmax 1.12 nmol min(-1) nmol P450(-1)) and produced nordexfenfluramine with small amounts of N-hydroxynordexfenfluramine. This is the first detailed study to examine the in-vitro metabolism of dexfenfluramine in human liver microsomes and by recombinant human P450s. We were able to identify CYP2D6 (high affinity) and CYP1A2 (low affinity) as the major enzymes catalysing the N-dealkylation of dexfenfluramine in human liver microsomes.

来源:Hazardous Substances Data Bank (HSDB)

代谢

右芬氟拉明已知的代谢物包括去甲右芬氟拉明。

Dexfenfluramine has known human metabolites that include nordexfenfluramine.

来源:NORMAN Suspect List Exchange

代谢

半衰期：17-20小时

Half Life: 17-20 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Dexfenfluramine与血清素再摄取泵结合。这导致血清素再摄取的抑制。血清素水平的增加导致血清素受体激活增加，进而导致位于下丘脑的摄食行为中枢的血清素能传递增强。这抑制了对碳水化合物的食欲。

Dexfenfluramine binds to the serotonin reuptake pump. This causes inhbition of serotonin reuptake. The increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates.

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

• 暴露途径

从胃肠道吸收良好。

Well-absorbed from the gastrointestinal tract.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括呼吸衰竭和心脏骤停，可能导致死亡。

Symptoms of overdose include respiratory failure and cardiac arrest leading to death.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

对于口服药物过量的总体支持性措施应当被实施。在右旋芬氟拉明过量案例中使用的措施包括胃内容物抽吸、用活性炭进行洗胃、渗透性利尿、强制酸性利尿，以及仔细监测中枢神经系统或呼吸抑制。透析的效果尚不清楚。患者应被密切监测，直到没有进一步药物相关中枢神经系统影响的证据。对于右旋芬氟拉明过量的特定治疗方法尚不清楚。(L1712)

General supportive measures for oral drug overdose should be instituted. Measures that have been used in dexfenfluramine overdose cases include aspiration of gastric contents, gastric lavage with activated charcoal, osmotic diuresis, forced acid diuresis, and careful monitoring of CNS or respiratory depression. The effectiveness of dialysis is not known. Patients should be followed closely until there is no further evidence of drug-related CNS effects. No specific therapy for dexfenfluramine overdose is known. (L1712)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

从胃肠道吸收良好。

Well-absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

尚不清楚盐酸右芬氟拉明是否会排入人乳中。但是，该药物会排入大鼠的乳汁中。

It is not known whether dexfenfluramine is excreted into human milk. However, the drug is excreted into rat milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

比较了10名肥胖患者（体重为理想体重的145 ± 13标准差%）和10名非肥胖健康志愿者（体重为理想体重的93 ± 8%）的右旋芬氟拉明（d-F）及其代谢物右旋去甲芬氟拉明（d-NF）的药代动力学。每个小组包括五名男性和五名女性，年龄为28 ± 8岁。受试者在不同时间接受单次静脉注射（15.5毫克基本药物，3小时内输注）和口服（胶囊中的25.9毫克基本药物）d-F。在肥胖受试者静脉输注后，d-F的分布体积（Vss）显著高于对照组（969.7 ± 393.3升；95%置信区间688.6-1250升与668.7 ± 139.6升；95%置信区间568.9-768.5升；P < 0.01）。清除率没有显著差异（43.9 ± 21.0升/小时对37.3 ± 10.6升/小时），终末半衰期倾向于更长（17.8 ± 9.4对13.5 ± 3.9小时，无统计学意义）。两组数据的综合表明，Vss与理想体重百分比（% IBW）之间存在正相关关系（r = 0.544；P < 0.02）。d-F的口服生物利用度在肥胖受试者为0.61 ± 0.15，在对照组为0.69 ± 0.11。肥胖受试者与对照组在Cmax、tmax和t1/2,z方面没有显著差异（Cmax：20.1 ± 6.7和27.3 ± 6.2微克/升；tmax：3.5对3.0；t1/2,z：16.5 ± 7.1对14.5 ± 2.6小时）。肥胖受试者中d-F/d-NF的AUC比例（以摩尔单位表示）为2.29 ± 1.78（静脉注射）对1.25 ± 0.64（口服），对照组为2.05 ± 1.26（静脉注射）对1.40 ± 0.87（口服）。

The pharmacokinetics of dexfenfluramine (d-F) and its metabolite dexnorfenfluramine (d-NF) were compared in 10 obese (145 + or - 13 s.d. % of ideal body weight (IBW)) and 10 non-obese healthy volunteers (93 + or - 8% IBW). Each group included five men and five women, aged 28 + or - 8 years. Subjects were given single doses of d-F i.v. (15.5 mg base infused over 3 hr) and orally (25.9 mg base in capsules) on separate occasions. After i.v. infusion in obese subjects, the volume of distribution (Vss) of d-F was significantly higher (969.7 + or - 393.3 l; 95% CI 688.6-1250 l) than in controls (668.7 + or - 139.6 l; 95% CI 568.9-768.5 l; P < 0.01). Clearance was not significantly different (43.9 + or - 21.0 l hr-1 vs 37.3 + or - 10.6 l hr-1) and the terminal half-life tended to be longer (17.8 + or - 9.4 vs 13.5 + or - 3.9 h NS). Combined data from the two groups indicated a positive correlation between Vss and % IBW (r = 0.544; P < 0.02). The oral bioavailability of d-F was 0.61 + or - 0.15 in obese subjects and 0.69 + or - 0.11 in controls. There was no significant difference between obese subjects and controls in Cmax, tmax and t1/2,z (Cmax: 20.1 + or - 6.7 and 27.3 + or - 6.2 micrograms l-1; tmax: 3.5 vs 3.0; t1/2,z: 16.5 + or - 7.1 vs 14.5 + or - 2.6 hr respectively). The AUC ratio expressed in molar units for d-F/d-NF was 2.29 + or - 1.78 (i.v.) vs 1.25 + or - 0.64 (oral) in obese subjects and 2.05 + or - 1.26 (i.v.) vs 1.40 + or - 0.87 (oral) in controls.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  右芬氟拉明 生成 N-Ethyl-N-[(S)-1-methyl-2-(3-trifluoromethyl-phenyl)-ethyl]-hydroxylamine
  参考文献：
  名称：

  1-芳基异丙基胺的伯和仲羟胺的旋光异构体的合成路线

  摘要：

  许多光学纯的初级1- arylisopropylamines的通过用相应的benzylimines的氧化转化为3-苯基-2-（1'-arylisopropyl）氧氮环丙烷米氯过苯甲酸。随后3-苯基氧氮丙啶的酸水解产生了光学纯的N-羟基-1-芳基异丙基胺。的作用米氯过苯甲酸对旋光纯的次要1- arylisopropylamines得到光学纯的N-羟基衍生物。通过使用N-三氟乙酰基-1-脯氨酰氯作为试剂的GLC分析羟胺的光学纯度。

  DOI：

  10.1016/0040-4020(75)87006-2
• 作为产物：
  描述：

  1-(3-(trifluoromethyl)phenyl)prop-2-en-1-ol 在 palladium on activated charcoal 吡啶 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 四氯化碳 、 硫酸 、 氢气 、 D-(-)-酒石酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 85.75h， 生成 右芬氟拉明
  参考文献：
  名称：

  无锐环氧化法不对称合成（S）-芬氟拉明

  摘要：

  我们描述了（S）芬氟拉明的一种合成及其前体（R）-和（S）-1-（间三氟甲基苯基）丙烷-2-醇的几种合成方法。它们是由伯烯丙基醇5的不对称环氧化和仲烯丙基醇6的不对称环氧化的动力学拆分获得的。

  DOI：

  10.1016/s0040-4020(01)80743-2

文献信息

• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• [EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
  申请人：AMGEN INC

  公开号：WO2013123444A1

  公开（公告）日：2013-08-22

  The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.

  本发明涉及与葡萄糖激酶调节蛋白相互作用的磺酰基化合物。此外，本发明涉及使用这些化合物或其药学上可接受的盐治疗2型糖尿病和其他涉及葡萄糖激酶调节蛋白的疾病和/或症状的方法，以及含有这些化合物或其药学上可接受的盐的药物组合物。
• Alkyl-containing 5-acylindolinones, the preparation thereof and their use as medicaments
  申请人：Heckel Armin

  公开号：US20050209302A1

  公开（公告）日：2005-09-22

  The present invention relates to alkyl-containing 5-acylindolinones of general formula wherein R 1 to R 3 are defined herein, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on protein kinases, particularly an inhibiting effect on the activity of glycogen synthase kinase (GSK-3).

  本发明涉及一般式的含烷基的5-酰基吲哚酮 其中R1至R3在此处定义，其互变异构体、对映异构体、非对映异构体、它们的混合物及其盐，具有有价值的药理特性，特别是对蛋白激酶具有抑制作用，特别是对糖原合成酶激酶（GSK-3）活性具有抑制作用。
• [EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK AS

  公开号：WO2005105736A1

  公开（公告）日：2005-11-10

  Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

  通用公式（I）的新化合物，这些化合物作为药物组成部分的用途，包括这些化合物的药物组成部分和使用这些化合物和组成部分的治疗方法。这些化合物可能在治疗和/或预防由过氧化物酶体增殖物激活受体（PPAR）介导的疾病中有用，特别是PPARδ亚型。
• [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。