埃索美拉唑 | 119141-88-7

• 物质功能分类: 原料药 - 消化系统用药 - 抑制胃酸分泌药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 埃索美拉唑
• 中文别名: 5-甲氧基-2-((S)-((4-甲氧基-3,5-二甲基-2-吡啶基)甲基)亚硫酰基)-1H-苯并咪唑；艾司奥美拉唑；5-甲氧基-2-((S)-((4-甲氧基-3,5-二甲基-2- 吡啶基)甲基)亚硫酰基)-1H-苯并咪唑；埃索米拉唑
• 英文名称: (S)-6-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]-sulfinyl]-1H-benzimidazole
• 英文别名: 5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole；(S)-6-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl)-1H-benzoimidazole；S(-)-5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole；(S)-omeprazole；S-omeprazole；esomeprazole；6-methoxy-2-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1H-benzimidazole
• CAS: 119141-88-7
• 化学式: C₁₇H₁₉N₃O₃S
• 分子量: 345.422
• InChiKey: SUBDBMMJDZJVOS-DEOSSOPVSA-N

物化性质

• 比旋光度：
  D20 -155° (c = 0.5 in chloroform)
• 沸点：
  600.0±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  DMF: 30 mg/ml,DMSO: 20 mg/ml,乙醇: 10 mg/ml,PBS (pH 7.2): 10 mg/ml
• 物理描述：
  Solid
• 熔点：
  155 °C
• 蒸汽压力：
  1.16X10-11 mm Hg at 25 °C (est)
• 亨利常数：
  Henry's Law constant = 3.04X10-19 atm-cu m/mol at 25 °C (est)
• 分解：
  Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx), Sulphur oxides, Magnesium oxide
• 解离常数：
  pKa = - 4.78 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

奥美拉唑在肝脏中被广泛代谢，主要通过细胞色素P450（CYP）酶系统。奥美拉唑的代谢产物缺乏抗分泌活性。奥美拉唑的大部分代谢依赖于CYP2C19同工酶，它形成了羟基和去甲基代谢物。剩余部分依赖于CYP3A4，形成亚砜代谢物。CYP2C19同工酶在奥美拉唑的代谢中表现出多态性，因为大约3%的高加索人和15到20%的亚洲人缺乏CYP2C19，被称为弱代谢者。然而，CYP2C19多态性的影响对于奥美拉唑来说不如奥美拉唑明显。在稳态下，弱代谢者的AUC与人群中其他人的AUC（广泛代谢者）的比例大约为2。在给予等摩尔剂量后，S-和R-异构体在肝脏中被不同地代谢，导致S-异构体的血浆水平高于R-异构体。已经检测到九种主要的尿液代谢物。两种主要代谢物被鉴定为羟基奥美拉唑和相应的羧酸。在血浆中已鉴定出三种主要代谢物：5-O-去甲基和亚砜衍生物以及羟基奥美拉唑。奥美拉唑的主要代谢物对胃酸分泌没有影响。

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP3A4 which forms the sulphone metabolite. CYP2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP2C19 and are termed Poor Metabolizers. However, the influence of CYP 2C19 polymorphism is less pronounced for esomeprazole than for omeprazole. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2. Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S- than of the R-isomer. Nine major urinary metabolites have been detected. The two main metabolites have been identified as hydroxyesomeprazole and the corresponding carboxylic acid. Three major metabolites have been identified in plasma: the 5-O-desmethyl- and sulphone derivatives and hydroxyesomeprazole. The major metabolites of esomeprazole have no effect on gastric acid secretion.

来源:DrugBank

代谢

奥美拉唑在肝脏中被细胞色素P450（CYP）酶系统广泛代谢。奥美拉唑的代谢物缺乏抗分泌活性。奥美拉唑的主要代谢部分依赖于CYP 2C19同工酶，它形成了羟基和去甲基代谢物。剩余部分依赖于CYP 3A4，形成亚砜代谢物。CYP 2C19同工酶在奥美拉唑的代谢中表现出多态性，因为大约3%的高加索人和15到20%的亚洲人缺乏CYP 2C19，被称为弱代谢者。在稳态下，弱代谢者的AUC与人群中其他部分（广泛代谢者）的AUC之比大约为2。在给予等摩尔剂量后，S-和R-异构体在肝脏中的代谢不同，导致S-异构体的血浆水平高于R-异构体。

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole's metabolism is dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP 3A4 which forms the sulphone metabolite. CYP 2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2. Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S- than of the R-isomer.

来源:Hazardous Substances Data Bank (HSDB)

代谢

埃索美拉唑已知的人类代谢物包括奥美拉唑砜、5-O-去甲基奥美拉唑和5-羟基奥美拉唑。

Esomeprazole has known human metabolites that include Omeprazole sulfone, 5-O-Desmethylomeprazole, and 5-Hydroxyomeprazole.

来源:NORMAN Suspect List Exchange

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：埃索美拉唑是质子泵抑制剂奥美拉唑的S-对映体。有限的信息表明，母亲每日剂量10毫克在乳汁中产生低水平，预计不会对哺乳婴儿造成任何不良影响。 ◉ 对哺乳婴儿的影响：一位母亲每天口服奥美拉唑20毫克，每天一次，在早晨服药后4小时泵奶并丢弃。她在剩下的时间里哺乳了3个月，然后断奶。婴儿在12个月大时仍然很好。 一位患有类风湿性关节炎的妇女接受口服埃索美拉唑10毫克、泼尼松2.5毫克和柳氮磺吡啶1克，每日一次，以及每2周注射200毫克的塞妥珠单抗。她的婴儿大约50%母乳喂养，50%配方奶喂养。婴儿没有出现可检测的药物相关不良反应。 ◉ 对泌乳和母乳的影响：据报道，奥美拉唑（消旋体形式）在几名男性中引起了男性乳房发育，并且在美国的一项回顾性索赔数据库研究中发现，质子泵抑制剂使用者患男性乳房发育的风险增加。 一篇综述文章报告称，对欧洲药物警戒中心数据库的搜索发现了45例男性乳房发育、9例乳汁分泌过多、19例乳房疼痛和12例乳房增大与埃索美拉唑有关。对世界卫生组织全球药物警戒数据库的搜索发现了114例男性乳房发育、38例乳汁分泌过多、56例乳房疼痛和28例乳房增大与埃索美拉唑有关。 一位妇女在开始每日一次服用40毫克埃索美拉唑治疗胃食管反流病一周后，出现血清催乳素和雌二醇升高以及双侧乳汁分泌过多。停用埃索美拉唑3天后，乳汁分泌过多消失，停用7天后催乳素和雌二醇恢复正常。一个月后，患者重新开始服用埃索美拉唑，并再次出现双侧乳汁分泌过多。她改用兰索拉唑后没有出现乳汁分泌过多。已建立泌乳的母亲催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Esomeprazole is the S-enantiomer of the proton-pump inhibitor, omeprazole. Limited information indicates that maternal doses of 10 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants. ◉ Effects in Breastfed Infants:One mother taking omeprazole 20 mg daily orally pumped and discarded her milk once each day 4 hours after her morning dose. She breastfed her infant the remainder of the day for 3 months before weaning. The infant remained well at 12 months of age. A woman with rheumatoid arthritis was treated with oral esomeprazole 10 mg, prednisone 2.5 mg and sulfasalazine 1 gram once daily as well as injections of certolizumab pegol 200 mg every 2 weeks. Her infant was about 50% breastfed and 50% formula fed. The infant had no detectable drug-related adverse effects. ◉ Effects on Lactation and Breastmilk:Omeprazole (the racemic form) has been reported to cause gynecomastia in several men and a retrospective claims database study in the United States found that users of proton pump inhibitors had an increased risk of gynecomastia. A review article reported that a search of database from the European Pharmacovigilance Centre found 45 cases of gynecomastia, 9 cases of galactorrhea, 19 cases of breast pain and 12 cases of breast enlargement associated with esomeprazole. A search of the WHO global pharmacovigilance database found 114 cases of gynecomastia, 38 cases of galactorrhea, 56 cases of breast pain and 28 cases of breast enlargement associated with esomeprazole. One woman developed elevated serum prolactin and estradiol with bilateral galactorrhea one week after starting esomeprazole 40 mg once daily for reflux esophagitis. The galactorrhea disappeared 3 days after discontinuing esomeprazole and prolactin and estradiol returned to normal 7 days after discontinuation. One month later, the patient restarted esomeprazole and again developed bilateral galactorrhea. She was switched to lansoprazole with no galactorrhea developing. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

在一项单次剂量研究中，同时给予奥美拉唑20毫克和硫糖铝1克，导致奥美拉唑吸收延迟，并使奥美拉唑的生物利用度降低16%。质子泵抑制剂应在给予硫糖铝至少30分钟前服用。

In a single-dose study, concomitant administration of omeprazole 20 mg and sucralfate 1 g resulted in delayed absorption of omeprazole and decreased omeprazole bioavailability by 16%. Proton-pump inhibitors should be administered at least 30 minutes before sucralfate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与奥美拉唑的药代动力学相互作用（降低利匹韦林在血浆中的浓度和AUC）。32 343 同时使用其他质子泵抑制剂也可能导致利匹韦林血浆浓度降低。343 利匹韦林与质子泵抑制剂同时使用是禁忌的。

Pharmacokinetic interaction with omeprazole (decreased plasma concentrations and AUC of rilpivirine).32 343 Concomitant use of other proton-pump inhibitors also may result in decreased plasma concentration of rilpivirine.343 Concomitant use of rilpivirine and proton-pump inhibitors is contraindicated.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

奥美拉唑40毫克每日一次与阿扎那韦（有或无低剂量利托那韦）的联合使用会导致阿扎那韦的血浆浓度显著降低，可能会失去抗逆转录病毒药物的治疗效果或产生药物耐药性。奥美拉唑40毫克每日一次（在阿扎那韦前2小时给药）和阿扎那韦400毫克每日一次的联合使用分别使阿扎那韦的AUC（药时曲线下面积）和峰浓度降低94%和96%。埃索美拉唑的制造商表示，不建议与阿扎那韦联合使用。如果阿扎那韦在未接受过抗逆转录病毒治疗的接受质子泵抑制剂的患者中使用，建议采用利托那韦增强的方案，即每日一次300毫克阿扎那韦与利托那韦100毫克，并随食物服用。质子泵抑制剂的剂量应在利托那韦增强的阿扎那韦前大约12小时给予；质子泵抑制剂的剂量不应超过奥美拉唑20毫克每日（或等效剂量）。在已接受过抗逆转录病毒治疗的患者中，不建议将质子泵抑制剂与阿扎那韦联合使用。

Concomitant use of omeprazole 40 mg once daily and atazanavir (with or without low-dose ritonavir) results in a substantial decrease in plasma concentrations of atazanavir and possible loss of the therapeutic effect of the antiretroviral agent or development of drug resistance. Concomitant use of omeprazole 40 mg once daily (administered 2 hours before atazanavir) and atazanavir 400 mg once daily decreased the AUC and peak plasma concentration of atazanavir by 94 and 96%, respectively. The manufacturer of esomeprazole states that concomitant administration with atazanavir is not recommended. If atazanavir is administered in an antiretroviral treatment-naive patient receiving a proton-pump inhibitor, a ritonavir-boosted regimen of 300 mg of atazanavir once daily with ritonavir 100 mg once daily with food is recommended. The dose of the proton-pump inhibitor should be administered approximately 12 hours before ritonavir-boosted atazanavir; the dose of the proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent). Concomitant use of proton-pump inhibitors with atazanavir is not recommended in antiretroviral treatment-experienced patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

奥美拉唑20毫克每日一次与地高辛在健康个体中的联合使用增加了地高辛的生物利用度10%（在某些个体中可增加至30%）。由于埃索美拉唑是奥美拉唑的对映体，预计埃索美拉唑与地高辛的联合使用将增加地高辛的系统暴露；因此，在此类联合使用期间可能需要监测地高辛中毒的表现。

Concomitant use of omeprazole 20 mg once daily and digoxin in healthy individuals increased digoxin bioavailability by 10% (up to 30% in some individuals). Because esomeprazole is an enantiomer of omeprazole, concomitant use of esomeprazole with digoxin is expected to increase systemic exposure to digoxin; therefore, monitoring for manifestations of digoxin toxicity may be required during such concomitant use.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

口服给药后，血浆峰浓度（Cmax）大约在1.5小时（Tmax）出现。当剂量增加时，Cmax成比例增加，从20毫克增加到40毫克，血浆浓度-时间曲线下面积（AUC）增加了三倍。在重复每日一次40毫克的剂量下，与单次40毫克剂量的64%相比，系统的生物利用度约为90%。平均暴露（AUC）从40毫克每日一次给药的第一天的4.32 μmol*hr/L增加到第五天的11.2 μmol*hr/L。与空腹状态相比，食物摄入后单次40毫克剂量奥美拉唑的AUC降低了43%至53%。奥美拉唑应在餐前至少一小时服用。与抗菌药物联合治疗：奥美拉唑镁40毫克每日一次与[DB01211] 500毫克每日两次和[DB01060] 1000毫克每日两次联合给药7天，用于17名健康男性和女性受试者。与单独使用奥美拉唑相比，三联联合治疗期间奥美拉唑的平均稳态AUC和Cmax分别增加了70%和18%。与克拉霉素和氨苄西林联合给药时奥美拉唑暴露的增加预计不会产生重大的安全问题。

After oral administration, peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 μmol*hr/L on Day 1 to 11.2 μmol*hr/L on Day 5 after 40 mg once daily dosing. The AUC after administration of a single 40 mg dose of Esomeprazole is decreased by 43% to 53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals. _Combination Therapy with Antimicrobials:_ Esomeprazole magnesium 40 mg once daily was given in combination with [DB01211] 500 mg twice daily and [DB01060] 1000 mg twice daily for 7 days to 17 healthy male and female subjects. The mean steady state AUC and Cmax of esomeprazole increased by 70% and 18%, respectively during triple combination therapy compared to treatment with esomeprazole alone. The observed increase in esomeprazole exposure during co-administration with clarithromycin and amoxicillin is not expected to produce significant safety concerns.

来源:DrugBank

吸收、分配和排泄

• 消除途径

奥美拉唑的血浆消除半衰期大约为1到1.5小时。不到1%的母药通过尿液排出。大约80%的口服奥美拉唑剂量以无活性代谢物的形式通过尿液排出，其余部分则以无活性代谢物的形式存在于粪便中。

The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.

来源:DrugBank

吸收、分配和排泄

• 分布容积

在健康志愿者中，稳态表观分布容积大约为16升。

The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

来源:DrugBank

吸收、分配和排泄

奥美拉唑的血浆消除半衰期大约为1到1.5小时。不到1%的母药通过尿液排出。大约80%的口服奥美拉唑剂量以无活性代谢物的形式通过尿液排出，其余部分则以无活性代谢物的形式存在于粪便中。

The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

奥美拉唑与血浆蛋白的结合率约为97%。在2至20微摩尔/升的浓度范围内，血浆蛋白结合率保持恒定。在健康志愿者中，稳态表观分布容积大约为16升。

Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 to 20 umol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温、密封、干燥

制备方法与用途

埃索美拉唑 介绍

埃索美拉唑是奥美拉唑的左旋异构体，是一种质子泵抑制剂，用于治疗多种胃肠道疾病。

药效学特性

埃索美拉唑通过特异性靶向作用机制减少胃酸分泌，为壁细胞中质子泵的特异性抑制剂。与奥美拉唑的R-异构体相比，其药效学特性相似。

适应症

1. 胃食管反流性疾病 (GERD)：包括糜烂性反流性食管炎、症状控制及根除幽门螺杆菌。
2. 十二指肠溃疡愈合与预防复发：与适当的抗菌疗法联合使用，可以根除幽门螺杆菌并促进愈合。

用法用量

1. 胃食管反流性疾病 (GERD)

   • 糜烂性反流性食管炎的治疗：40mg 每日一次，连服四周。
   • 食管炎未治愈或持续有症状者：再服药治疗四周。
   • 已经治愈的食管炎患者防止复发的长期维持治疗：20mg 每日一次。
   • 无食管炎患者的症状控制：20mg 每日一次，如4周后症状未缓解，则需进一步检查。之后可采用即时疗法：需要时口服 20mg ，每日一次。

2. 与幽门螺杆菌相关的消化性溃疡治疗：

   • 埃索美拉唑片 20 mg + 阿莫西林 1 g + 克拉霉素 500mg ，每日二次，共7天。

药物相互作用

• 埃索美拉唑可降低酮康唑和伊曲康唑的吸收。
• 与经CYP2C19酶代谢的药物（如地西泮、西酞普兰、丙米嗪、氯米帕明和苯妥英）合用时，应减少剂量并监测血浆浓度。

不良反应

• 常见：头痛、腹痛、腹泻、腹胀、恶心/呕吐、便秘。
• 少见：皮炎、瘙痒、荨麻疹、头昏、口干。

生产方法

埃索美拉唑通过从奥美拉唑拆分得到。

以上信息为埃索美拉唑的基本概述，具体使用时应遵医嘱。

反应信息

• 作为反应物：
  描述：

  埃索美拉唑 在 potassium hydroxide 作用下， 以 甲醇 、 丁酮 为溶剂， 生成 esomeprazole potassium
  参考文献：
  名称：

  [EN] A METHOD OF MANUFACTURING (S)-5-METHOXY-2-[[(4-METHOXY-3,5-DIMETHYL-2- PYRIMIDINYL)METHYL]SULFINYL]-1H-BENZIMIDAZOLE USING A CHIRAL COMPLEX WITH MANDELIC ACID
  [FR] PROCÉDÉ DE FABRICATION DE (S)-5-MÉTHOXY-2-[[(4-MÉTHOXY-3,5-DIMÉTHYL-2-PYRIDINYL)MÉTHYL]SULFINYL]-1H-BENZIMIDAZOLE À L'AIDE D'UN COMPLEXE CHIRAL AVEC DE L'ACIDE MANDÉLIQUE

  摘要：

  这项发明涉及一种新的制造方法，用于制造公式（I）的（S）-5-甲氧基-2-[[(4-甲氧基-3,5-二甲基-2-吡啶基)甲基]磺酰基]-1H-苯并咪唑及其通式（II）的盐，其中通式（III）的磺化物在由手性苯乙酸的手性官能衍生物构成的配体的手性金属络合物催化剂的存在下被过氧化氢氧化。

  公开号：

  WO2011120475A1
• 作为产物：
  描述：

  奥美拉唑 在 Escherichia coli DMSO reductase 作用下， 以 甲醇 、 aq. phosphate buffer 为溶剂， 反应 3.0h， 以98%的产率得到
  参考文献：
  名称：

  手性亚砜的酶动力学拆分–对映体互补方法†

  摘要：

  描述了一种新的用于制备手性亚砜的酶促测定方法，该方法与甲硫氨酸亚砜还原酶A（MsrA）的已知的（S）-对映异构体还原活性是对映体互补的。为此，我们利用了DMSO还原酶（DmsABC），该酶最近被我们发现在固定相大肠杆菌中高度上调。

  DOI：

  10.1039/c9cc05470g
• 作为试剂：
  描述：

  埃索美拉唑 、 3-氯苯甲酸 、 、 sodium hydroxide 在 二氯甲烷 、 N,N-二甲基甲酰胺 、 水 、 埃索美拉唑 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 生成 (5)6-Methoxy-2-[[(4-methoxy-3,6-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1H-benzimidazole
  参考文献：
  名称：

  Granulated pharmaceutical formulations and methods for making the same

  摘要：

  本发明揭示了由公式（Ia）表示的化合物，以及与其相关的组合物和复合物，可选择与公式（Ib）的化合物结合。还揭示了制备和使用这些化合物的药物配方和方法。

  公开号：

  US06653329B1

文献信息

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• [EN] HETEROCYCLIC AMIDES USEFUL AS PROTEIN MODULATORS<br/>[FR] AMIDES HÉTÉROCYCLIQUES UTILES EN TANT QUE MODULATEURS DE PROTÉINE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017175147A1

  公开（公告）日：2017-10-12

  Disclosed are compounds having the formula (I-N), wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, and R17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.

  揭示了具有化学式（I-N）的化合物，其中q、r、s、A、B、C、RA1、RA2、RB1、RB2、RC1、RC2、R3、R4、R5、R6、R14、R15、R16和R17如本文所定义，或其互变异构体，或其盐，特别是其药用可接受盐。
• [EN] MODULATORS OF STIMULATOR OF INTERFERON GENES (STING) USEFUL IN TREATING HIV<br/>[FR] MODULATEURS DE STIMULATEUR DES GÈNES (STING) D'INTERFÉRON UTILES DANS LE TRAITEMENT DU VIH
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019069269A1

  公开（公告）日：2019-04-11

  Disclosed are compounds having the formula: (I-N) wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, and R17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof, along with combinations thereof, all of which are useful in HIV therapies.

  揭示了具有以下式的化合物：(I-N)其中q、r、s、A、B、C、RA1、RA2、RB1、RB2、RC1、RC2、R3、R4、R5、R6、R14、R15、R16和R17如本文所定义，或其互变异构体，或其盐，特别是其药用可接受盐，以及其组合物，所有这些在HIV疗法中是有用的。
• [EN] COMBINATIONS OF INHIBITORS OF IRAK4 WITH INHIBITORS OF BTK<br/>[FR] COMBINAISONS D'INHIBITEURS DE L'IRAK4 À L'AIDE D'INHIBITEURS DE LA BTK
  申请人：BAYER PHARMA AG

  公开号：WO2016174183A1

  公开（公告）日：2016-11-03

  The present application relates to novel combinations of at least two components, component A and component B: · component A is an IRAK4-inhibiting compound of the formula (I) as defined herein, or a diastereomer, an enantiomer, a metabolite, a salt, a solvate or a solvate of a salt thereof; · component B is a BTK-inhibiting compound, or a pharmaceutically acceptable salt thereof; and, optionally, · one or more components C which are pharmaceutical products; in which one or two of the above-defined compounds A and B are optionally present in pharmaceutical formulations ready for simultaneous, separate or sequential administration, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of endometriosis, lymphoma, macular degeneration, COPD, neoplastic disorders and psoriasis.

  本申请涉及至少两种组分的新型组合，组分A和组分B：·组分A是根据本文所定义的式(I)的IRAK4抑制化合物，或其对映体、对映异构体、代谢物、盐、溶剂合物或其盐的溶剂合物；·组分B是BTK抑制化合物，或其药学上可接受的盐；以及，可选地，·一种或多种组分C，它们是药用产品；其中上述定义的化合物A和B中的一种或两种可选择地存在于用于治疗和/或预防疾病的制剂中，准备用于同时、分开或顺序给药，用于治疗和/或预防疾病，以及用于生产用于治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防子宫内膜异位症、淋巴瘤、黄斑变性、慢性阻塞性肺病、肿瘤性疾病和牛皮癣。