(R)-2-(2-氧代吡咯烷-1-基)丁酰胺 | 103765-01-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (R)-2-(2-氧代吡咯烷-1-基)丁酰胺
• 中文别名: 左乙拉西坦杂质D；(R)-左乙拉西坦
• 英文名称: levetiracetam
• 英文别名: (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide；(R)-2-(2-oxopyrrolidin-1-yl)butyramide；2-(2-oxopyrrolidin-1-yl)butanamide；ucbL060；L060；(R)-α-ethyl-2-oxo-1-pyrrolidineacetamide；(2R)-2-(2-oxopyrrolidin-1-yl)butanamide
• CAS: 103765-01-1
• 化学式: C₈H₁₄N₂O₂
• 分子量: 170.211
• InChiKey: HPHUVLMMVZITSG-ZCFIWIBFSA-N

物化性质

• 熔点：
  114-116 °C(Solv: acetone (67-64-1))
• 沸点：
  395.9±25.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于丙酮（少量，超声处理）、氯仿（少量）、甲醇（少量）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

利伐昔罗（24%的剂量）的主要代谢途径是乙酰胺基团的酶促水解。未检测到CYP450代谢。 消除途径：百分之六十六（66%）的剂量以原形通过肾脏排泄。这些代谢物没有已知的药理活性，并通过肾脏排泄。排泄机制是肾小球滤过，随后部分肾小管重吸收。 半衰期：6-8小时

The major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. No CYP450 metabolism detected. Route of Elimination: Sixty-six percent (66%) of the dose is renally excreted unchanged. The metabolites have no known pharmacological activity and are renally excreted. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. Half Life: 6-8 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

利维昔兰发挥其抗癫痫效果的精确机制尚不清楚。利维昔兰的抗癫痫活性在多种动物癫痫发作模型中进行了评估。利维昔兰并未抑制由最大电刺激或不同化学致惊剂引起的单次癫痫发作，并且在亚最大刺激和阈值测试中仅表现出最小的活性。然而，观察到对由毛果芸香碱和卡因酸两种化学致惊剂引起的、模仿人类复杂部分性癫痫发作继发全身性活动的局灶性癫痫发作的保护作用。利维昔兰在大鼠的点燃模型中也显示出抑制特性，这是一种人类复杂部分性癫痫的模型，无论是在点燃发展过程中还是在完全点燃状态下。这些动物模型对特定类型人类癫痫的预测价值尚不确定。利维昔兰被认为可以刺激突触囊泡蛋白2A（SV2A），抑制神经递质的释放。

The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Levetiracetam did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Levetiracetam also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. The predictive value of these animal models for specific types of human epilepsy is uncertain. Levetiracetam is thought to stimulate synaptic vesicle protein 2A (SV2A), inhibiting neurotransmitter release.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

可能会导致一种可能发展成史蒂文斯-约翰逊综合征的危险性皮疹，这是一种极为罕见但可能致命的皮肤病。

May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：在一些女性中，母乳中的左乙拉西坦（levetiracetam）水平可能相对较高，有时会导致母乳喂养的婴儿出现镇静和其他不良反应。如果母亲需要左乙拉西坦，这并不一定是要停止母乳喂养的理由。然而，应该监测婴儿是否出现嗜睡、适当的体重增加和发育里程碑，特别是在较年轻的、完全母乳喂养的婴儿中，以及在使用多种抗癫痫药物组合时。如果药物在怀孕和哺乳期间持续使用，那么在产后期早期进行母体血清水平监测和剂量调整是可取的。一些证据表明，左乙拉西坦可能会减少一些女性的母乳供应。 ◉ 对母乳喂养婴儿的影响：一位患有癫痫的妇女在怀孕期间服用了苯妥英钠和丙戊酸。她在产后第3天开始母乳喂养，并在产后第7天出现了癫痫发作。开始使用左乙拉西坦（剂量未报告），婴儿变得越发低张力，并且喂养困难。停止母乳喂养后，婴儿从医院出院时状况良好。 在怀孕和哺乳期间，7位完全母乳喂养的婴儿的母亲平均每天服用2430毫克（范围1500至3500毫克/天）的左乙拉西坦，并联合使用各种其他抗癫痫药物，在整个6至8周的研究期间，研究人员认为婴儿看起来很健康。第八位部分母乳喂养的婴儿的母亲在怀孕后9个月开始服用左乙拉西坦，并在10个月大时看起来很健康。 在母亲每天服用1000至3000毫克左乙拉西坦的情况下，10位4至23天大的新生儿在母乳喂养期间没有报告不良反应。其中4位母亲还在服用拉莫三嗪；1位在服用卡马西平；还有一位在服用替加宾、氯巴占和奥卡西平。 一位长期患有癫痫的妇女在怀孕期间服用普里米酮和左乙拉西坦。她的药物剂量在怀孕期间被减少，以提供左乙拉西坦血清浓度为40.5毫克/升和普里米酮（苯巴比妥）血清浓度为3.4毫克/升。指示母亲在3天后停止母乳喂养。第二天，她的婴儿出现了戒断性癫痫。重新开始母乳喂养后，婴儿的癫痫发作停止，并且没有复发。婴儿没有异常发现，并且在6个月大时健康成长，没有癫痫发作。 在里昂，法国的药物警戒中心，18位哺乳母亲在服用左乙拉西坦并在哺乳前打电话咨询的情况下，她们的婴儿（包括3位早产儿）与18位对照婴儿进行了配对。平均剂量为每天1000毫克（范围500至3000毫克/天），其中8位至少在服用另一种抗癫痫药物。母乳喂养的中位持续时间为40天（范围10至224天），其中13位新生儿完全母乳喂养。母乳喂养的婴儿中位随访时间为9.1个月（范围0.75至73个月）。一位25天大的婴儿，母亲每天服用3000毫克左乙拉西坦加氯巴占，因嗜睡、呕吐和体重减轻而住院，停止母乳喂养后迅速好转。另一个接触左乙拉西坦和氯巴占的婴儿体重增长不良，但这似乎是由乳汁产量不足引起的。除了这些婴儿外，所有服用左乙拉西坦的婴儿和控制组婴儿都正常生长和发育。 一位孕妇在怀孕8周时出现鼻窦血块和2个小脑室内出血，随后出现癫痫持续状态。她接受了左乙拉西坦1000毫克和拉科酰胺100毫克每天两次的治疗，以及剩余怀孕期和产后期使用依诺肝素和拉贝洛尔。她的婴儿在36周妊娠时出生，并在生命的前几天大约50%的时间进行母乳喂养。婴儿表现出嗜睡和喂养不良，但暂停母乳喂养并没有改善婴儿的状况。在产后15天停止母乳喂养后，婴儿逐渐好转。婴儿在7个月大时表现出正常的发育。 一位患有癫痫的母亲在母乳喂养婴儿期间每天服用左乙拉西坦2000毫克加拉科酰胺200毫克每天两次。她母乳喂养（喂养程度未说明）她的婴儿7个月，婴儿在24个月大时没有不良反应。 在一项对20位服用左乙拉西坦的母亲和她们的21位婴儿的研究中，3位服用左乙拉西坦单药治疗，每天剂量分别为3750、3000和1500毫克的妇女报告了她们的完全母乳喂养婴儿出现嗜睡。改为部分母乳喂养后，嗜睡很快消失。另外14位服用左乙拉西坦单药治疗的母亲和3位联合使用钠伐普仑、拉科酰胺或托吡酯的母亲没有报告不良反应。所有参与研究的母亲（n=21）的婴儿都有适当的体重增长。 ◉ 对泌乳和母乳的影响：在一项研究中，18位服用

◉ Summary of Use during Lactation:Levels of levetiracetam in milk can be relatively high in some women and can occasionally cause sedation and other adverse effects in their breastfed infants. If levetiracetam is required by the mother, it is not necessarily a reason to discontinue breastfeeding. However, the infant should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsants. Maternal serum level monitoring and dosage adjustment is advisable in the early postpartum period if the drug was taken throughout pregnancy and breastfeeding. Some evidence suggests that levetiracetam might reduce the maternal breastmilk supply in some women. ◉ Effects in Breastfed Infants:A woman with epilepsy took phenytoin and valproic acid during pregnancy. She began breastfeeding on day 3 postpartum and had a seizure on day 7 postpartum. Levetiracetam (dosage not reported) was started and the infant became increasingly hypotonic and nursed poorly. Breastfeeding was discontinued and the infant was discharged from the hospital in a healthy condition. Seven exclusively breastfed infants whose mothers were taking an average dosage of 2430 mg daily (range 1500 to 3500 mg daily) of levetiracetam plus various other anticonvulsants during pregnancy and lactation appeared healthy to the investigators throughout the 6 to 8 week study period. An eighth partially breastfed infant whose mother was taking valproate and oxcarbazepine started taking levetiracetam 9 months postpartum appeared healthy at 10 months of age. No adverse effects were reported in 10 newborns who were 4 to 23 days old who were breastfed during maternal intake of levetiracetam 1000 to 3000 mg daily. Four mothers were also taking lamotrigine; 1 was taking carbamazepine; and one was taking tiagabine, clobazam and oxcarbazepine. A woman with long-standing seizure disorder was taking primidone and levetiracetam became pregnant. The dosage of her medications were reduced during pregnancy to provide a levetiracetam serum concentration of 40.5 mg/L and a primidone (phenobarbital) serum concentration of 3.4 mg/L. The mother was instructed to discontinue breastfeeding after 3 days. The following day her infant developed withdrawal seizures. After reinstituting breastfeeding, the infant's seizures stopped and did not recur. The infant had no abnormal findings and was thriving and seizure free at 6 months of age. The infants (including 3 preterm) of 18 nursing mothers who were taking levetiracetam and called the Pharmacovigilance Center in Lyon, France before breastfeeding were paired with 18 control infants. The median dosage was 1000 mg daily (range 500 to 3000 mg daily) and 8 were receiving at least one additional anticonvulsant. The median duration of breastfeeding was 40 days (range 10 to 224 days), and 13 newborns were exclusively breastfed. Breastfed infants were followed for a median of 9.1 months (range 0.75 to 73 months). One 25-day-old infant whose mother was taking levetiracetam 3000 mg daily plus clobazam was hospitalized for sedation, vomiting, and weight loss, and improved rapidly after breastfeeding discontinuation. Another infant exposed to levetiracetam and clobazam had poor weight gain, but it appeared to be caused by poor milk production. Other than these infants, all levetiracetam and control infants grew and developed normally. A pregnant woman suffered blood clots in the sinuses and 2 small intracranial hemorrhages followed by status epilepticus at 8 weeks of gestation. She was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Her infant was delivered at 36 weeks gestation and about 50% breastfed for the first days of life. The infant was sleepy and fed poorly, but pauses in breastfeeding did not improve the infant's condition. Breastfeeding was discontinued at 15 days postpartum and the infant gradually improved. The infant showed normal development at 7 months of age. A mother with epilepsy took levetiracetam 2000 mg daily plus lacosamide 200 mg twice daily while breastfeeding their infants. She breastfed (extent not stated) her infant for 7 months with no infant adverse effects at 24 months of age. A pregnant woman suffered blood clots in the sinuses and 2 small intracranial hemorrhages followed by status epilepticus at 8 weeks of gestation. She was treated with levetiracetam 1000 mg and lacosamide 100 mg twice daily as well as enoxaparin and labetalol for the rest of her pregnancy and postpartum. Her infant was delivered at 36 weeks gestation and about 50% breastfed for the first days of life. The infant was sleepy and fed poorly, but pauses in breastfeeding did not improve the infant's condition. Breastfeeding was discontinued at 15 days postpartum and the infant gradually improved. The infant showed normal development at 7 months of age. Lacosamide and levetiracetam were probably the cause of the infant's sedation and poor feeding. In a study of 20 mothers taking levetiracetam and their 21 infants, 3 women taking levetiracetam monotherapy in daily doses of 3750, 3000 and 1500 mg reported drowsiness in their fully breastfed infants. Drowsiness resolved shortly after switching to partial breastfeeding. No adverse effects were reported by 14 other mothers who were on levetiracetam monotherapy, and 3 mothers who were on polytherapy with sodium valproate, lacosamide, or topiramate. All the infants (n = 21) of the mothers participating in the study had age-appropriate weight gain. ◉ Effects on Lactation and Breastmilk:In a study of mothers taking levetiracetam during breastfeeding, 7 of 18 mothers discontinued or reduced breastfeeding because of poor milk output. The infant of one mother taking 3000 mg of levetiracetam daily plus clobazam had poor weight gain at day 15 of life. A retrospective study of 102 women with epilepsy found that women taking levetiracetam were more likely to initiate and continue breastfeeding at 3 months postpartum than women taking lamotrigine.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 暴露途径

口服给药后迅速且几乎完全吸收（99%）。在空腹受试者口服给药后约一小时达到血浆峰浓度。

Rapidly and almost completely absorbed after oral administration (99%). Peak plasma concentrations occurring in about an hour following oral administration in fasted subjects.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  乙酰乙酸乙酯 、 (R)-2-(2-氧代吡咯烷-1-基)丁酰胺 在 diphenylammonium triflate 作用下， 以 甲苯 为溶剂， 反应 8.0h， 以78%的产率得到(Z)-ethyl 3-(2-(2-oxopyrrolidin-1-yl)butanamido)but-2-enoate
  参考文献：
  名称：

  Highly efficient and facile synthesis of β-enaminones catalyzed by diphenylammonium triflate

  摘要：

  二苯胺三氟甲磺酸盐作为有机催化剂在合成各种取代β-二酮和酰胺（或胺）的β-烯胺酮中的催化性能得到了评估。在温和的反应条件下，广泛范围的β-烯胺酮以良好至优异的产率有效合成。将二苯胺三氟甲磺酸盐（DPAT）作为催化剂使得这一方案成本效益高、腐蚀性低且易于操作。

  DOI：

  10.1007/s11696-019-00838-2
• 作为产物：
  描述：

  左乙拉西坦 在 sodium methylate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 24.0h， 生成 (R)-2-(2-氧代吡咯烷-1-基)丁酰胺
  参考文献：
  名称：

  左乙拉西坦和依替西坦α-酮戊二酸共晶体的特殊情况：获得稳定的依替西坦团聚体

  摘要：

  在这一贡献中，我们证明了通过与左旋乙酰胺（一种用于治疗癫痫的手性促智药物）共结晶，可以获得固态的α-酮戊二酸（AKGA）的乳糖醇互变异构体。此外，我们表明可以与外消旋的左乙拉西坦，依替西坦（Eti）外消旋等效物分离出共晶体，其中AKGA保持在酮形式。我们还报告了在Etiracetam–AKGA系统中存在共晶凝聚物，它在室温下比外消旋共晶更稳定。稳定的团块的存在与左乙拉西坦共晶体的对映体特异性有关，这很可能与依替西坦对映异构体一次稳定一种内酯互变异构体或通过氢键促进其形成的能力有关。

  DOI：

  10.1021/acs.cgd.6b00819

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] SUBSTITUTED N-HETEROCYCLIC CARBOXAMIDES AS ACID CERAMIDASE INHIBITORS AND THEIR USE AS MEDICAMENTS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
  申请人：BIAL BIOTECH INVEST INC

  公开号：WO2021055627A1

  公开（公告）日：2021-03-25

  The invention provides substituted N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

  这项发明提供了替代的N-杂环羧酰胺和相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病（例如癌症、溶酶体贮积症、神经退行性疾病、炎症性疾病）的方法。
• [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] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
  申请人：D'Sidocky Neil R.

  公开号：US20080242694A1

  公开（公告）日：2008-10-02

  Provided herein are Heterocyclic Compounds having the following structure: wherein R 1 , R 2 , X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.

  本文提供具有以下结构的杂环化合物： 其中R1、R2、X、Y和Z如本文所定义，包含有效量杂环化合物的组合物，以及治疗或预防癌症、炎症性疾病、免疫疾病、代谢性疾病以及通过给予患者需要的有效量杂环化合物来抑制激酶途径治疗或预防的疾病的方法。