右旋苯丙胺 | 51-64-9

• 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: 右旋苯丙胺
• 中文别名: 右旋苯丙胺右旋安非他命；右苯丙胺
• 英文名称: dexamfetamine
• 英文别名: d-amphetamine；dextroamphetamine；dexamphetamine；(S)-amphetamine；(2S)-1-phenylpropan-2-amine
• CAS: 51-64-9
• 化学式: C₉H₁₃N
• 分子量: 135.209
• InChiKey: KWTSXDURSIMDCE-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

右旋安非他命通过肝脏中的细胞色素P-450 2D6代谢为4-羟基安非他命，随后通过磺基转移酶或葡萄糖醛酸转移酶进行结合。

Dextroamphetamine is metabolized by cytochrome P-450 2D6 in the liver to 4-hydroxyamphetamine and later conjugated by sulfotransferase or glucoronyltransferase.

来源:DrugBank

代谢

在兔体内产生N-乙酰安非他命。在兔和豚鼠体内产生苯甲基甲酮肟。/根据表格/

Yields N-acetylamphetamine in rabbit. Benzyl methyl ketoxime in rabbit & guinea pig. /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠和狗中产生对羟基右旋安非他命。/根据表格/

Yields p-hydroxy-d-amphetamine in rat & dog. /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

苯丙胺是一种非儿茶酚类、拟交感神经胺，其中枢神经系统刺激作用比肾上腺素和其他儿茶酚胺类更强。盐酸利司他明是一种前药，在通过肠道和/或肝脏的首过代谢转化为右旋苯丙胺之前，几乎没有任何药理活性。拟交感神经非儿茶酚胺的灭活主要依赖于单胺氧化酶的分解，由于在α-碳原子上用烷基取代氢可以阻止氨基团的酶促灭活，因此α-取代可以延长非儿茶酚胺的作用时间（但儿茶酚胺的作用时间不会延长，因为它们主要通过不同的机制灭活）。苯丙胺的芳香环上缺少羟基，减少了药物在胃肠道中的灭活，因此苯丙胺类药物口服后仍具有活性。

Amphetamine is a noncatechol, sympathomimetic amine and has a greater CNS stimulant activity than epinephrine and other catecholamines. Lisdexamfetamine dimesylate is a prodrug and has little, if any, pharmacologic activity until converted to dextroamphetamine by first-pass intestinal and/or hepatic metabolism. Inactivation of sympathomimetic noncatecholamines largely depends on breakdown by monoamine oxidase and since substitution of an alkyl group for hydrogen on the a-carbon atom blocks enzymatic inactivation of the amino group, the duration of action of noncatecholamines (but not of catecholamines, which are inactivated largely by a different mechanism) is prolonged by a-substitution. The absence of a hydroxyl group on the aromatic ring of amphetamine reduces inactivation of the drug in the GI tract and the amphetamines are active following oral administration.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在兔体内产生N-甲基-D-苯丙胺。在兔体内产生α-甲基-β-苯乙基羟基胺。/根据表格/

Yields N-methyl-d-amphetamine in rabbit. Alpha-methyl-beta-phenethylhydroxylamine in rabbit. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：硫酸右旋安非他命是一种精神刺激剂，是安非他命的苯乙胺衍生物。它用于治疗发作性睡病和儿童的过度活跃状态。它可能被滥用于提高性能、缓解疲劳。这种药物口服或注射滥用非常常见。人类暴露和毒性：主要风险包括急性中枢神经系统刺激、导致心动过速、心律失常、高血压和心血管崩溃的心脏毒性。依赖和滥用的高风险。心血管效应包括：心悸、胸痛、心动过速、心律失常和高血压；在严重中毒时可能会发生心血管崩溃。心肌缺血、梗死和心室功能障碍已有描述。中枢神经系统效应包括：中枢神经系统刺激、震颤、不安、激动、失眠、活动过度、头痛、惊厥、昏迷和反射亢进。已观察到中风和脑动脉炎。消化道效应包括：呕吐、腹泻和痉挛。慢性甲基安非他命滥用已发生急性短暂性缺血性结肠炎。泌尿生殖系统效应包括：膀胱括约肌张力增加可能导致排尿困难、犹豫和急性尿潴留。脱水和横纹肌溶解可能导致肾衰竭。可能注意到肾缺血和暂时性高甲状腺素血症。增加的代谢和肌肉活动可能导致过度换气和体温升高。慢性使用常见体重减轻。已报告低钾血症和高钾血症。脱水很常见。可能注意到肌束震颤和僵直。横纹肌溶解是严重安非他命中毒的重要后果。激动、混乱、情绪高涨、警觉性增加、健谈、易怒和恐慌发作是典型的。慢性滥用可导致幻觉和偏执。在慢性使用后突然停药会发生戒断综合症。厌食、失眠、精神病态人格障碍、自杀倾向、图雷特综合症和其他障碍、甲状腺功能亢进、窄角青光眼、糖尿病和心血管疾病如心绞痛、高血压和心律失常。在成人中：由于个体差异和耐受性的发展，毒性剂量差异很大。儿童似乎比成人更易感，且不太可能已发展出耐受性。用于医疗指征的安非他命对胎儿的先天性异常没有显著风险。安非他命通常似乎不是人类致畸物。新生儿可能出现轻微的戒断症状，但对婴儿随访的少数研究没有显示长期后遗症。孕妇非法使用或滥用安非他命对胎儿和新生儿构成重大风险，包括宫内生长迟缓、早产和增加母体、胎儿和新生儿发病率的潜力。在子宫内暴露于安非他命的新生儿发生的大脑损伤似乎与安非他命的血管收缩性质直接相关。追踪了65名在怀孕期间至少在第一季度对安非他命上瘾的儿童的母亲。智力、心理功能、生长和身体健康在八岁时都在正常范围内，但在整个孕期暴露的儿童倾向于更具攻击性。动物研究：d-安非他命减少了鸽对视觉刺激持续时间的辨别的准确性。在猕猴和狒狒中，d-安非他命减少了对视觉和听觉刺激的反应时间。然而，这种效果是剂量依赖性的，在较高剂量后，反应时间的增加占主导地位。在猴子中，d-安非他命在掩蔽听觉阈值的掩蔽听觉阈值或亮度辨别没有变化的情况下，减少了反应时间。然而，在松鼠猴中，d-安非他命产生了适度的掩蔽听觉阈值增加。

IDENTIFICATION AND USE: Dexamphetamine sulfate is a psychostimulant and phenylethylamine derivative of amphetamine. It is used for treatment of narcolepsy and hyperkinetic states in children. It can be misused for performance enhancement, relief of fatigue. Abuse of this drug either orally or by injection is extremely common. HUMAN EXPOSURE AND TOXICITY: Main risks include acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning. Myocardial ischemia, infarction and ventricular dysfunction were described. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects including: increased bladder sphincter tone which may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia and transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Anorexia, insomnia, psychopathic personality disorders, suicidal tendencies, Gilles de la Tourette syndrome and other disorders, hyperthyroidism, narrow angle glaucoma, diabetes mellitis and cardiovascular diseases such as angina, hypertension and arrythmias. In adults: the toxic dose varies considerably due to individual variations and the development of tolerance. Children appear to be more susceptible than adults and are less likely to have developed tolerance. The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. Cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. Sixty five children were followed whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: d-Amphetamine decreased the accuracy of visual stimulus duration discriminations in pigeons. In both rhesus monkeys and baboons d-amphetamine decreases reaction times to visual and auditory stimuli. This effect was dose dependent, however, with increases in reaction time predominating after higher doses. The decreased reaction times following d-amphetamine occur in the absence of changes in size discrimination thresholds or brightness discrimination in the monkey. In the squirrel monkey, however, d-amphetamine produced modest increases in masked auditory thresholds.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

作用机制尚不清楚。右旋安非他命刺激中枢肾上腺素能受体释放去甲肾上腺素。在较高剂量下，它通过反转单胺转运体，从腹侧盖皮层多巴胺系统和黑质纹状体多巴胺系统释放多巴胺。右旋安非他命可能还直接激活中枢5-HT受体，并可能抑制单胺氧化酶（MAO）。在周围，人们认为安非他命通过作用于肾上腺素能神经末梢和α-和β-受体来引起去甲肾上腺素的释放。调节血清素途径可能有助于产生镇静作用。

The exact mechanism of action is not known. Dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dosages, it causes release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems by reversal of the monoamine transporters. Dextroamphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：右旋安非他命

Compound:dextroamphetamine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：没有匹配项

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

右旋安非他命的生物利用度数据不易获得，但是无论是在饭前还是饭后服用，生物利用度都没有差异。

Bioavailability data of dextroamphetamine is not readily available, however there is no difference in bioavailability when taken with or without a meal.

来源:DrugBank

吸收、分配和排泄

• 消除途径

药物的三分之一通过肾脏消除。

A third of the drug is eliminated renally.

来源:DrugBank

吸收、分配和排泄

• 分布容积

195升。

195L.

来源:DrugBank

吸收、分配和排泄

• 清除

17升/小时。

17L/h.

来源:DrugBank

吸收、分配和排泄

安非他明类药物容易从胃肠道吸收，其效果可持续4-24小时。安非他明分布到身体的大多数组织中，在大脑和脑脊液（CSF）中浓度较高。口服给药后大约3小时，安非他明出现在尿液中。安非他明的尿液排泄依赖于pH值，酸性尿液中排泄量增加。给人类口服消旋安非他明后，大约相等的两种异构体在前12小时内被排泄；12小时后，d-异构体的排泄比例持续减少。口服给予70毫克的放射性标记剂量 的利他林（右旋安非他明的前药）后，96%的剂量在尿液中回收；回收的放射性中，42%的剂量与安非他明相关，25%与马尿酸相关，2%与母药相关。右旋安非他明和左旋安非他明（在美国已不再商业销售）似乎有不同的代谢命运，但药物命运与其药理活性之间的关系尚未确定。有一些数据显示安非他明及其异构体的立体特异性代谢，但立体特异性尿液排泄似乎不太可能。

Amphetamines are readily absorbed from the GI tract and effects persist for 4-24 hours. Amphetamines are distributed into most body tissues with high concentrations occurring in the brain and cerebral spinal fluid (CSF). Amphetamine appears in the urine within about 3 hours following oral administration. Urinary excretion of the amphetamines is pH-dependent and excretion is enhanced in acidic urine. Following oral administration of racemic amphetamine to humans, approximately equal amounts of both isomers were excreted during the first 12 hours; after the first 12 hours, a continually decreasing proportion of the d-isomer was excreted. Following oral administration of a 70-mg radiolabeled dose of lisdexamfetamine (a prodrug of dextroamphetamine), 96% of the dose was recovered in the urine; of the recovered radioactivity, 42% of the dose was related to amphetamine, 25% to hippuric acid, and 2% to the parent drug. Dextroamphetamine and levamfetamine (no longer commercially available in the US) appear to have different metabolic fates, but the relationship between the fate of the drugs and their pharmacologic activity has not been determined. There are some data to indicate stereospecific metabolism of amphetamine and its isomers, but stereospecific urinary excretion appears unlikely.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  右旋苯丙胺 在 硫酸 作用下， 以 水 为溶剂， 反应 0.05h， 以93%的产率得到硫酸苯丙胺
  参考文献：
  名称：

  METHOD FOR MAKING PHARMACEUTICAL COMPOUNDS

  摘要：

  制备B式苯乙胺的方法：其中R2、R3、R4、R5、R6、Rα、Rβ和Rn分别独立地选自氢、烷基、酰基、芳基、酰胺、氨基酸、糖和核苷酸。该方法包括在无碱的情况下还原A式化合物的步骤：其中R2、R3、R4、R5、R6、Rα、Rβ和Rn如上所定义。

  公开号：

  US20100125146A1
• 作为产物：
  描述：

  硫酸苯丙胺 在 sodium hydroxide 作用下， 生成 右旋苯丙胺
  参考文献：
  名称：

  相关气相色谱和蒸腾作用评估（d）-苯丙胺和几种伯胺在T / K = 298时的汽化焓和蒸气压

  摘要：

  通过蒸腾研究测量了几种脂族和苯基取代的伯胺在T / K = 298.15时的蒸气压，并计算了它们的蒸发焓。将结果与兼容的文献值相结合，以通过相关气相色谱法评估（d）-苯异丙胺的蒸发焓和蒸气压。将结果与外消旋苯丙胺的估计值或测量值进行比较。T / K = 298.15时的蒸发焓和蒸气压通过蒸腾量（kJ·mol –1，p/ Pa）：1-庚胺，（49.75±0.38，291）；1-辛胺（55.05±0.29，108）; 1-癸胺，（64.94±0.32，12）; 苄胺（54.32±0.32，88）; （dl）-α-甲基苄胺，（55.26±0.33，82）; 2-苯乙胺（57.51±0.35，43）。这些材料中的几种用作标准品会导致（d）-苯异丙胺在T / K = 298.15（58.2±2.7）kJ mol –1和（38±12）Pa时的蒸发焓和蒸气压。

  DOI：

  10.1021/je400212t
• 作为试剂：
  描述：

  (±)-3-羟基十四烷酸 在 右旋苯丙胺 作用下， 生成 (R)-(-)-3-羟基十四烷酸
  参考文献：
  名称：

  An Agent from E. coli Causing Hemorrhage and Regression of an Experimental Mouse Tumor. III. The Component Fatty Acids of the Phospholipide Moiety¹

  摘要：

  DOI：

  10.1021/ja01101a007

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] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS QUINUCLIDINE EN TANT QUE LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016073407A1

  公开（公告）日：2016-05-12

  There are disclosed a series of quinuclidines having the Formula (I). which bind to the nicotinic α7 receptor and may be useful for the treatment of disorders of the central nervous system.

  揭示了一系列具有化学式（I）的喹诺啉类化合物，它们与尼古丁型α7受体结合，可能对中枢神经系统疾病的治疗有用。
• [EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2009151744A1

  公开（公告）日：2009-12-17

  The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.

  本发明涉及基于巯基和S-亚硝基巯基的SNO化合物及其衍生物，以及它们在治疗正常呼吸控制缺失方面的用途，包括治疗与睡眠、肥胖、某些药物和其他医疗状况相关的呼吸暂停和低通气。
• [EN] NOVEL ANTIVIRAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS ANTIVIRAUX
  申请人：UNIV LEUVEN KATH

  公开号：WO2014170368A1

  公开（公告）日：2014-10-23

  The present invention relates to a series of novel compounds and derivatives thereof, methods to prevent or treat viral infections by using the novel compounds, processes for their preparation, their use to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, preferably infections with viruses belonging to the family of the Togaviridae and more preferably infections with chikungunya virus (CHIKV).

  本发明涉及一系列新化合物及其衍生物，利用这些新化合物预防或治疗病毒感染的方法，以及它们的制备过程，用于治疗或预防病毒感染以及用于制造治疗或预防病毒感染的药物，最好是用于治疗属于Togaviridae家族的病毒，更好地是用于治疗寨卡病毒感染。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。

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