Aminophylline | 95646-60-9

• 物质功能分类: 原料药 - 呼吸系统用药 - 平喘药
• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Aminophylline
• 英文别名: 1,3-dimethyl-7H-purine-2,6-dione;ethane-1,2-diamine
• CAS: 95646-60-9；317-34-0
• 化学式: C16H24N10O4
• 分子量: 420.43
• InChiKey: FQPFAHBPWDRTLU-UHFFFAOYSA-N

物化性质

• 熔点：
  269-270 °C
• 溶解度：
  H2O: 3.7 mg/mL 溶液应新鲜配制。
• LogP：
  -0.175 (est)
• 颜色/状态：
  White or slightly yellowish granules or powder
• 气味：
  Slight ammoniacal
• 味道：
  Bitter
• 稳定性/保质期：

  Stable under recommended storage conditions.

• 分解：
  When heated to decomp it emits toxic fumes of /nitrogen oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  -3.18
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  191
• 氢给体数：
  4
• 氢受体数：
  8

ADMET

代谢

茶碱生物转化的N-去甲基化和羟基化途径都是受限于代谢能力的。由于茶碱代谢速率的个体间差异较大，一些患者在血清茶碱浓度低于10 mcg/mL时，消除过程可能会出现非线性。由于这种非线性导致剂量变化时血清茶碱浓度的变化不成比例，因此建议在调整剂量时采取小幅度递增或递减，以实现血清茶碱浓度的预期变化。无法准确预测患者茶碱代谢的剂量依赖性，但初始清除率非常高（即，在高于平均剂量时血清茶碱浓度较低）的患者在剂量变化时最有可能经历血清茶碱浓度的大幅变化。/茶碱/

Both the N-demethylation and hydroxylation pathways of theophylline biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of theophylline metabolism, non-linearity of elimination may begin in some patients at serum theophylline concentrations <10 mcg/mL. Since this non-linearity results in more than proportional changes in serum theophylline concentrations with changes in dose, it is advisable to make increases or decreases in dose in small increments in order to achieve desired changes in serum theophylline concentrations. Accurate prediction of dose-dependency of theophylline metabolism in patients a priori is not possible, but patients with very high initial clearance rates (i.e., low steady-state serum theophylline concentrations at above average doses) have the greatest likelihood of experiencing large changes in serum theophylline concentration in response to dosage changes. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

咖啡因和3-甲基黄嘌呤是唯一具有药理活性的茶碱代谢物。3-甲基黄嘌呤的药理活性大约是茶碱的十分之一，正常肾功能成年人的血清浓度小于1微克/毫升。在终末期肾病患者中，3-甲基黄嘌呤可能会积累到接近未代谢茶碱浓度的水平。无论肾功能如何，成年人的咖啡因浓度通常是检测不到的。在新生儿中，咖啡因可能会积累到接近未代谢茶碱浓度的水平，从而产生药理作用。/茶碱/

Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of theophylline and serum concentrations in adults with normal renal function are <1 ug/mL. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized theophylline concentration. Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized theophylline concentration and thus, exert a pharmacologic effect. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

茶碱由肝脏代谢为1,3-二甲基尿酸、1-甲基尿酸和3-甲基黄嘌呤。... 不同个体对茶碱的代谢速率不同；但是，药物的个人代谢通常是可重复的。茶碱及其代谢物主要通过肾脏排出。然而，茶碱的肾清除率仅占茶碱总体血浆清除率的8-12%。少量未经改变的茶碱随粪便排出。/茶碱/

Theophylline is metabolized by the liver to 1,3-dimethyluric acid, 1-methyluric acid, and 3-methylxanthine. ... Individuals metabolize theophylline at different rates; however, individual metabolism of the drug is generally reproducible. Theophylline and its metabolites are excreted mainly by the kidneys. Renal clearance of the drug, however, contributes only 8-12% of the overall plasma clearance of theophylline. Small amounts of theophylline are excreted in feces unchanged. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

茶碱通过微粒体细胞色素P450系统进行代谢，主要由同工酶CYP1A2催化。主要代谢途径是去甲基化成为3-甲基黄嘌呤，此外还会被去甲基化或氧化成其他代谢物。小于10%的茶碱以原形从尿液中排出。/茶碱/

Theophylline is metabolized via the microsomal cytochrome p450 system, primarily by the isozyme CYP1A2. The major pathway is demethylation to 3-methylxanthine in addition to being demethylated or oxidized to other metabolites. Less than 10% of theophylline is excreted in the urine unchanged. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在成人及一岁以上的儿童中，大约90%的茶碱剂量在肝脏中被代谢。生物转化通过去甲基化生成1-甲基黄嘌呤和3-甲基黄嘌呤，以及羟基化生成1,3-二甲基尿酸。1-甲基黄嘌呤进一步通过黄嘌呤氧化酶羟基化生成1-甲基尿酸。大约6%的茶碱剂量会发生N-甲基化生成咖啡因。茶碱去甲基化生成3-甲基黄嘌呤是由细胞色素P-450 1A2催化的，而细胞色素P-450 2E1和P-450 3A3催化羟基化生成1,3-二甲基尿酸。去甲基化生成1-甲基黄嘌呤似乎是由细胞色素P-450 1A2或与之密切相关的一种细胞色素催化的。在新生儿中，N-去甲基化途径缺失，而羟基化途径的功能明显不足。这些途径的活性在一年内逐渐增加到最大水平。/茶碱/

Following oral dosing, theophylline does not undergo any measurable first-pass elimination. In adults and children beyond one year of age, approximately 90% of the dose is metabolized in the liver. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Theophylline demethylation to 3-methylxanthine is catalyzed by cytochrome P-450 1A2, while cytochromes P-450 2E1 and P-450 3A3 catalyze the hydroxylation to 1,3-dimethyluric acid. Demethylation to 1-methylxanthine appears to be catalyzed either by cytochrome P-450 1A2 or a closely related cytochrome. In neonates, the N-demethylation pathway is absent while the function of the hydroxylation pathway is markedly deficient. The activity of these pathways slowly increases to maximal levels by one year of age. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：氨茶碱是白色或略带黄色的颗粒或粉末。氨茶碱是由茶碱和水合二胺制备而成。它被用作支气管扩张剂。人类暴露和毒性：氨茶碱可以在没有已知潜在癫痫或增加癫痫发作风险因素的病人中诱发癫痫。这些癫痫大多数难以控制，与其他药物毒性相比被低估。尽管氨茶碱诱发癫痫在临床上有着悠久的历史，但人们对甲基黄嘌呤诱导癫痫产生的潜在分子机制知之甚少。在成年人中，氨茶碱导致死亡通常发生在静脉注射大剂量氨茶碱时，特别是在有肾、肝或心血管并发症的病人中。在其他病人中，注射的快速性而非使用的剂量似乎是诱发急性低血压、癫痫、昏迷、心脏停搏、心室颤动和死亡的重要因素。因此，静脉注射氨茶碱或茶碱应该缓慢进行。在儿童中，死亡通常是由于过量服用和对茶碱对中枢神经系统刺激的高度敏感。有一些关于氨茶碱过敏反应的报告，大多数病例在英文文献中是迟发型反应。然而，大多数日本病例是速发型。乙酰化是二胺的主要代谢途径。大多数日本人有快速或中速乙酰化者，而高加索人有50%的可能性是慢速乙酰化者。这种差异表明日本和高加索人在氨茶碱过敏反应的速发和迟发反应发生率上有所不同。氨茶碱治疗可能与心肌酶水平升高有关。在体外，氨茶碱通过灭活半胱天冬酶3和8来保护MRC-5细胞的凋亡。动物研究：氨茶碱（100-250 mg/kg）在小鼠中一致地诱发癫痫和发作后死亡，传统的抗惊厥药和腺苷激动剂对其无效。对大脑匀浆的生化分析显示，氨茶碱癫痫与大脑丙二醛和一氧化氮代谢物水平的增强有关，而超氧化物歧化酶活性降低，这些变化在褪黑素和L-NAME预处理后得到缓解。氨茶碱在大鼠中以剂量依赖性方式诱发惊厥，癫痫发生率和死亡率在300 mg/kg时达到最大，自由基生成显著增加。抗氧化剂预处理对氨茶碱诱导的自由基生成显示出不同的缓解效果，但它们在对抗氨茶碱诱导的癫痫和发作后死亡方面几乎无效。在怀孕的兔子中，氨茶碱治疗并没有加速一般解剖肺发育，反映在肺气腔容量与肺组织重量的比率上。在类似的实验条件下，母体咖啡因治疗对胎儿兔肺没有影响。在另一项实验中，从交配后的第二十五天开始，给怀孕的母兔静脉注射氨茶碱（6 mg/kg/天），在第二十八天通过子宫切开术取出胎儿。一组新生儿呼吸空气，另一组呼吸100%氧气。在新生儿动物自然或人工通气期间评估肺力学，特别是参照肺泡体积密度的组织学。氨茶碱处理的小鼠体重更大，存活率提高，肺灌洗液中的磷脂酰甘油含量增加。在空气中呼吸的氨茶碱处理动物呼吸频率增加，但关于肺顺应性的数据显示，处理组和对照组之间没有显著差异。结论是，氨茶碱的有益效果主要归因于加速胎儿生长和改善出生后呼吸调节的组合，而不是对肺的生物化学和功能成熟的具体影响。氨茶碱加剧了发育中的大鼠大脑因癫痫损伤而造成的损害。

IDENTIFICATION AND USE: Aminophylline is white or slightly yellowish granules or powder. Aminophylline is prepared from theophylline and aqueous ethylenediamine. It is used as bronchodilator agent. HUMAN EXPOSURE AND TOXICITY: Aminophylline can trigger seizures in patients without known underlying epilepsy or added risk factor for seizure exacerbation in epilepsy. Most of these seizures are difficult to control and are underappreciated compared to other drug toxicities. Despite a long clinical history of aminophylline-induced seizures, relatively little is known about the underlying molecular mechanisms that contribute to methylxanthine-induced seizure generation. Fatalities in adults have generally occurred during or following IV administration of large doses of aminophylline in patients with renal, hepatic, or cardiovascular complications. In other patients, the rapidity of the injection, rather than the dose used, appears to be the more important factor precipitating acute hypotension, seizures, coma, cardiac standstill, ventricular fibrillation, and death. IV aminophylline or theophylline should therefore be given slowly. In children, fatalities usually are a result of overdosage and marked sensitivity to the CNS stimulation of theophylline. There are some reports of aminophylline hypersensitivity reaction and the most cases were delayed type reaction in English literatures. However, most of Japanese cases were immediate type. Acetylation is a main metabolic pathway of ethylenediamine. Most of Japanese have a rapid or intermediate acetylators on the other hand. Caucasian have a 50% likelihood of being slow acetylators. This difference suggest the different incidences of immediate and delayed reaction of aminophylline hypersensitivity reaction in Japanese and Caucasian respectively. Aminophylline treatment might be associated with elevated levels of myocardial enzymes. In vitro, aminophylline protected apoptosis of MRC-5 cells through the inactivation of caspases 3 and 8. ANIMAL STUDIES: Aminophylline (100-250 mg/kg) consistently induced seizures and post-ictal mortality in mice, and conventional anticonvulsants and adenosine agonists were ineffective in antagonizing them. Biochemical assay of brain homogenates showed that aminophylline seizures were associated with enhancements in brain malone dialdehyde and nitric oxide metabolites levels, whereas, superoxide dismutase activity was reduced, and these changes were attenuated after melatonin and L-NAME pretreatment. Aminophylline induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg and there was significant increase of free radical generation. Pre-treatment with antioxidants showed differential attenuating effects on aminophylline induced free radical generation, but they were very much ineffective in antagonizing aminophylline induced seizures and post-seizure mortality by any appreciable extent. In pregnant rabbits, aminophylline treatment produced no acceleration in general anatomic lung development, as reflected in the ratio of lung air-space capacity to lung tissue weight. Under similar experimental conditions, maternal caffeine treatment had no effect on fetal rabbit lungs. In other experiment, pregnant rabbit does were treated intravenously with aminophylline (6 mg/kg/day) from the twenty-fifth day after the day of mating, and the fetuses were delivered by hysterotomy on the twenty-eighth day. One group of neonates was breathing air, and another group 100% oxygen. Lung mechanics were evaluated in the newborn animals during spontaneous or artificial ventilation, and the lungs were studied histologically with particular reference to the alveolar volume density. Aminophylline-treated litters had greater body weights, an improved survival rate, and an increased amount of phosphatidylglycerol in lung lavage fluid. Respiratory frequency was increased in aminophylline-treated animals breathing air, but data on lung compliance showed no significant difference between treated and control animals. It was concluded that the beneficial effect of aminophylline can be attributed largely to a combination of accelerated fetal growth and improved postnatal regulation of breathing and less to a specific influence on the biochemical and functional maturation of the lung. Aminophylline, exacerbated seizure-induced damage in the developing brain in rats.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物：氨茶碱

Compound:aminophylline

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：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：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 分布容积

0.3到0.7升/千克

0.3 to 0.7 L/kg

来源:DrugBank

吸收、分配和排泄

• 清除

出生后3-15天：0.29 mL/kg/min 出生后25-57天：0.64 mL/kg/min 1-4岁：1.7 mL/kg/min 4-12岁：1.6 mL/kg/min 13-15岁：0.9 mL/kg/min 16-17岁：1.4 mL/kg/min 成年（16-60岁），非吸烟哮喘患者：0.65 mL/kg/min 老年人（>60岁），肝肾功能：0.41 mL/kg/min 急性肺水肿：0.33 mL/kg/min 慢性阻塞性肺病（COPD）>60岁，稳定非吸烟>1年：0.54 mL/kg/min 慢性阻塞性肺病伴肺心病：0.48 mL/kg/min 囊性纤维化（14-28岁）：1.25 mL/kg/min 肝病 - 胆汁淤积：0.31 mL/kg/min 肝硬化：0.35 mL/kg/min 急性肝炎：0.65 mL/kg/min 感染性休克伴多器官衰竭：0.47 mL/kg/min 甲状腺功能减退：0.38 mL/kg/min 甲状腺功能亢进：0.8 mL/kg/min

0.29 mL/kg/min [postnatal age 3-15 days] 0.64 mL/kg/min [postnatal age 25-57 days] 1.7 mL/kg/min [ 1-4 years] 1.6 mL/kg/min [4-12 years] 0.9 mL/kg/min [13-15 years] 1.4 mL/kg/min [16-17 years] 0.65 mL/kg/min [Adults (16-60 years), non-smoking asthmatics] 0.41 mL/kg/min [Elderly (>60 years). liver, and renal function] 0.33 mL/kg/min [Acute pulmonary edema] 0.54 mL/kg/min [COPD->60 years, stable non-smoker >1 year] 0.48 mL/kg/min [COPD with cor pulmonale] 1.25 mL/kg/min [Cystic fibrosis (14-28 years)] 0.31 mL/kg/min [Liver disease -cholestasis] 0.35 mL/kg/min [cirrhosis] 0.65 mL/kg/min [acute hepatitis] 0.47 mL/kg/min [Sepsis with multi-organ failure] 0.38 mL/kg/min [hypothyroid] 0.8 mL/kg/min [hyperthyroid]

来源:DrugBank

吸收、分配和排泄

静脉注射氨茶碱产生最高和最快的血清茶碱浓度。在健康成年人中，单次静脉注射氨茶碱（约为5 mg/kg，在30分钟内完成），平均血清茶碱峰值浓度可达到大约10 ug/mL。

IV theophylline produces the highest and most rapid serum theophylline concentration. Following a single IV dose of theophylline (as aminophylline) of about 5 mg/kg over 30 minutes to healthy adults, mean peak serum theophylline concentrations of about 10 ug/mL are reached.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在新生儿中，大约50%的茶碱剂量以原形从尿液中排出。在生命的前三个月之后，大约10%的茶碱剂量以原形从尿液中排出。/茶碱/

In neonates, approximately 50% of the theophylline dose is excreted unchanged in the urine. Beyond the first three months of life, approximately 10% of the theophylline dose is excreted unchanged in the urine. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当通过肌内注射给药时，茶碱通常吸收缓慢且不完全。肛门栓剂（在美国已不再商业供应）无论其栓剂基质是亲水性的还是亲脂性的，都会被缓慢且不规则地吸收。/茶碱/

When administered IM, theophylline is usually absorbed slowly and incompletely. Rectal suppositories (no longer commercially available in the US) are slowly and erratically absorbed, regardless of whether the suppository base is hydrophilic or lipophilic. /Theophylline/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  6.1(b)

制备方法与用途

根据提供的信息,我总结了氨茶碱的主要内容:

1. 适应症:

• 支气管哮喘、哮喘型慢性支气管炎等呼吸系统疾病
• 急性心功能不全、心脏性哮喘
• 胆绞痛等

2. 不良反应:恶心、呕吐、失眠、焦虑不安等轻度症状,严重可导致抽搐、昏迷等。

3. 用法用量:

• 口服常用量:成人0.1-0.2g/次,tid;儿童3-5mg/kg/d,tid
• 注射剂给药剂量需按说明书或医嘱使用

4. 规格:氨茶碱片、肠溶片、缓释片以及注射液等。

5. 化学性质:白色或淡黄色颗粒粉末,易溶于水。

6. 生产方法:将茶碱与乙二胺复盐反应制得。

7. 注意事项:

• 心脏病患者慎用
• 不宜过量使用以免引起中毒

8. 中毒表现及处理:血浓度>25mg/L可诊断为中毒,需立即停药并给予对症治疗。

总之,氨茶碱是一种常用的平喘、强心药物,但应谨慎使用以避免不良反应和中毒风险。

反应信息

• 作为反应物：
  描述：

  Aminophylline 生成 二苯并[f,h]喹诺西林
  参考文献：
  名称：

  ISHIGURO, YOSHINOBU;SAWADA, MASARU;OHMAYU, KAZUYO;KAWABE, KIYOSHI, J. PHARM. SOC. JAP., 1982, 102, N 2, 211-214

  摘要：

  DOI：
• 作为产物：
  描述：

  茶碱 、 乙二胺 生成 Aminophylline
  参考文献：
  名称：

  KAWASHIMA, Y.;AOKI, S.;TAKENAKA, H.;MIYAKE, Y., J. PHARM. SCI., 1984, 73, N 10, 1407-1410

  摘要：

  DOI：

文献信息

• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• IRAK DEGRADERS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20190192668A1

  公开（公告）日：2019-06-27

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用这些化合物的方法。
• SUBSTITUTED INDOLES
  申请人：Gant Thomas G.

  公开号：US20090191183A1

  公开（公告）日：2009-07-30

  Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了Formula I的替代吲哚半胱氨酸白三烯受体调节剂，其制备方法，药物组合物以及使用方法。