红霉素 | 114-07-8

• 物质功能分类: 原料药 - 抗生素类药物 - 大环内酯类药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 红霉素
• 中文别名: 红霉素碱；艾狄密新
• 英文名称: erythromycin
• 英文别名: erythromycin A；Ery；erythrocin；erythromycine；erithromycin；erthromycin；erytromycin；e-mycin；eryc；ERM；(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 114-07-8
• 化学式: C₃₇H₆₇NO₁₃
• mdl: MFCD00084654
• 分子量: 733.938
• InChiKey: ULGZDMOVFRHVEP-RWJQBGPGSA-N

物化性质

• 熔点：
  133 °C
• 比旋光度：
  -74.5 º (c=2, ethanol)
• 沸点：
  719.69°C (rough estimate)
• 密度：
  1.1436 (rough estimate)
• 溶解度：
  可溶于乙醇
• 物理描述：
  Solid
• 颜色/状态：
  Hydrated crystals from water
• 气味：
  Odorless
• 味道：
  Bitter
• 蒸汽压力：
  2.12X10-25 mm Hg at 25 °C (est)
• 水溶性：
  -3.2
• 旋光度：
  Specific optical rotation: -78 deg at 25 °C/D (c = 1.99 in ethanol)
• 分解：
  When heated to decomp it emits toxic fumes of /nitric oxides./
• 解离常数：
  pKa = 8.9
• 碰撞截面：
  258.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  51
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.945
• 拓扑面积：
  194
• 氢给体数：
  5
• 氢受体数：
  14

ADMET

代谢

肝脏首过代谢对口服剂量后红霉素的代谢有显著贡献。红霉素部分通过CYP3A4酶代谢为N-去甲基红霉素。红霉素也可以水解成脱水形式（脱水红霉素[AHE]和其他代谢物），这一过程在酸性条件下被促进。AHE对微生物无效，但能抑制肝脏药物氧化，因此被认为是红霉素药物相互作用的重要影响因素。

Hepatic first-pass metabolism contributes significantly to erythromycin metabolism after an oral dose. Erythromycin is partially metabolized by CYP3A4 enzyme to N-desmethylerythromycin. Erythromycin is also hydrolyzed to _anhydro_ forms (anhydroerythromycin [AHE] and other metabolites), and this process is promoted by acidic conditions. AHE is inactive against microbes but inhibits hepatic drug oxidation and is therefore considered to be an important contributor to erythromycin drug-drug interactions.

来源:DrugBank

代谢

大鼠口服给药10毫克红霉素后20小时，在大肠及粪便中回收了大约37-43%的给药放射性，27.2至36.1%在尿液中，21-29%在呼出气体中。红霉素在肝脏中被迅速代谢，主要是通过去甲基化过程，并以去甲基红霉素的形式从胆汁中排出，这种主要代谢物只存在于大鼠的胆汁和大肠内容物中。异构甲基团以二氧化碳的形式在呼出气体中消除。

Twenty hours after an oral administration of 10 mg erythromycin to rats, about 37-43% of the administered radioactivity was recovered in the intestinal tract plus feces, 27.2 to 36.1% in the urine, 21-29% in the expired air. It was rapidly metabolized in the liver, mainly through demethylation process, and excreted in the bile as des-N-methyl-erythromycin, the major metabolite present only in the bile and in the intestinal contents of rats. The isotropic methyl group was eliminated in the expired air as CO2.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏。广泛代谢 - 口服给药后，尿液中可以回收不到5%的给药剂量的活性形式。红霉素部分通过CYP3A4代谢，导致许多药物相互作用。 半衰期：0.8 - 3小时

Hepatic. Extensively metabolized - after oral administration, less than 5% of the administered dose can be recovered in the active form in the urine. Erythromycin is partially metabolized by CYP3A4 resulting in numerous drug interactions. Half Life: 0.8 - 3 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

红霉素通过穿透细菌细胞膜并与细菌核糖体的50 S亚单位或接近“P”或供体位点可逆地结合，从而阻止tRNA（转移RNA）与供体位点的结合。阻止了从“A”或受体位点到“P”或供体位点的肽链移位，随后的蛋白质合成被抑制。红霉素仅对活跃分裂的生物体有效。红霉素减少寻常痤疮病变的确切机制尚不完全清楚：然而，这种效果部分似乎是由于药物的抗菌活性。

Erythromycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the “P” or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the “A” or acceptor site to the “P” or donor site is prevented, and subsequent protein synthesis is inhibited. Erythromycin is effective only against actively dividing organisms. The exact mechanism by which erythmromycin reduces lesions of acne vulgaris is not fully known: however, the effect appears to be due in part to the antibacterial activity of the drug.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

红霉素治疗与治疗期间血清酶水平升高率低（1%至2%）有关。酶水平升高通常是无症状和短暂的，可能不比安慰剂或其他比较抗生素治疗更常见。 红霉素引起的临床上明显的肝损伤是罕见的，但由于使用频率高，红霉素在过去几年中一直是药物诱导肝损伤最常见的原因之一。最初，人们认为肝损伤在使用红霉素酯时更为常见，或者可能仅限于红霉素酯。然而，几乎所有红霉素制剂都有黄疸和肝损伤的报道，对损伤的交叉敏感性是常见的，尽管并非普遍存在。红霉素的肝毒性与其他大环内酯类抗生素描述的相似，通常是一种温和且自限性的胆汁淤积性肝炎。开始使用红霉素与肝损伤发病之间的潜伏期很短，通常为1到3周，并且较短（ 与红霉素使用相关的一个独立综合征是急性右上象限疼痛，不伴有黄疸，通常在开始治疗的一两天内出现。血清酶可能轻度升高，通常以肝细胞模式出现，并在停止使用红霉素后迅速恢复。 可能性评分：A（临床上明显肝损伤的已知原因）。

Erythromycin therapy is associated with a low rate (1% to 2%) of serum enzyme elevations during therapy. The enzyme elevations are typically asymptomatic and transient, and may occur no more frequently than with placebo or other comparator anitbiotic treatments. Clinically apparent liver injury from erythromycin is rare, but because of the frequency of its use, erythromycin has been one of the most common causes of drug induced liver injury at least in previous years. Initially, liver injury was thought to be more common with, or perhaps limited to, erythromycin estolate. However, instances of jaundice and liver damage have been reported with virtually all formulations of erythromycin, and cross sensitivity to injury is common, although not universal. The hepatotoxicity of erythromycin resembles that described in other macrolide antibiotics and is typically a mild and self-limiting cholestatic hepatitis. The latency period between starting erythromycin and onset of liver injury is short, typically 1 to 3 weeks and is shorter ( A separate syndrome associated with erythromycin use is acute right upper quadrant pain without jaundice that arises within a day or two of starting therapy. Serum enzymes may be mildly elevated, usually in a hepatocellular pattern and with rapid recovery once erythromycin is stopped. Likelihood score: A (well known cause of clinically apparent liver injury).

来源:LiverTox

毒理性

• 药物性肝损伤

化合物：红霉素

Compound:erythromycin

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

药物性肝损伤标注：最令人关注的药物性肝损伤

DILI Annotation:Most-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重等级：5

Severity Grade:5

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

口服红霉素容易被吸收。食物摄入似乎对红霉素的血药浓度没有影响。不同个体对红霉素吸收存在一些差异，这可能不同程度地影响吸收。红霉素的Cmax（最高血药浓度）为1.8微克/升，Tmax（达到最高浓度的时间）为1.2小时。在一项药代动力学研究中，口服500毫克红霉素后的血清AUC（药时曲线下面积）为7.3±3.9毫克·小时/升。红霉素在口服给药后生物利用度变化较大（18-45%）以及其在酸性条件下容易分解的特点广为人知。

Orally administered erythromycin is readily absorbed. Food intake does not appear to exert effects on serum concentrations of erythromycin. Some interindividual variation exists in terms of erythromycin absorption, which may impact absorption to varying degrees. The Cmax of erythromycin is 1.8 mcg/L and the Tmax is 1.2 hours. The serum AUC of erythromycin after the administration of a 500mg oral dose was 7.3±3.9 mg.h/l in one pharmacokinetic study. Erythromycin is well known for a bioavailability that is variable (18-45%) after oral administration and its susceptibility to broken down under acidic conditions.

来源:DrugBank

吸收、分配和排泄

• 消除途径

在肝功能正常的患者中，红霉素在肝脏中浓缩，然后通过胆汁排出。口服给药的红霉素剂量中，不到5%会在尿液中排出。大部分被吸收的红霉素去向不明，但很可能是被代谢了。

In patients with normal liver function, erythromycin concentrates in the liver and is then excreted in the bile.Under 5% of the orally administered dose of erythromycin is found excreted in the urine. A high percentage of absorbed erythromycin is not accounted for, but is likely metabolized.

来源:DrugBank

吸收、分配和排泄

• 分布容积

红霉素可出现在大多数体液中并在白细胞和炎症液体中积聚。尽管红霉素在脊髓液中的浓度较低，但是当患有脑膜炎时，红霉素通过血脑屏障的扩散会增加，这可能是由于存在容易被渗透的炎症组织。红霉素可以穿过胎盘。

Erythromycin is found in most body fluids and accumulates in leucocytes and inflammatory liquid. Spinal fluid concentrations of erythromycin are low, however, the diffusion of erythromycin through the blood-brain barrier increases in meningitis, likely due to the presence of inflamed tissues which are easily penetrated. Erythromycin crosses the placenta.

来源:DrugBank

吸收、分配和排泄

• 清除

在健康受试者中，服用125毫克静脉剂量的红霉素后，其清除率为0.53 ± 0.13升/小时/千克。在一项针对健康患者和肝硬化患者的临床研究中，严重肝硬化患者的红霉素清除率显著降低。肝硬化患者的清除率为42.2 ± 10.1升/小时，而健康患者的清除率为113.2 ± 44.2升/小时。

The clearance of erythromycin in healthy subjects was 0.53 ± 0.13 l/h/kg after a 125mg intravenous dose. In a clinical study of healthy patients and patients with liver cirrhosis, clearance of erythromycin was significantly reduced in those with severe liver cirrhosis. The clearance in cirrhotic patients was 42.2 ± 10.1 l h–1 versus 113.2 ± 44.2 l h-1 in healthy patients.

来源:DrugBank

吸收、分配和排泄

口服给药的erythromycins主要在小肠的前段即十二指肠被吸收。药物的生物利用度是可变的，取决于包括特定的红霉素衍生物、给药剂型的配方、衍生物的酸稳定性、消化道中的食物存在以及胃排空时间等多个因素。

Absorption of orally administered erythromycins occurs mainly in the duodenum. The bioavailability of the drugs is variable and depends on several factors including the particular erythromycin derivative, the formulation of the dosage form administered, acid stability of the derivative, presence of food in the GI tract, and gastric emptying time.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  3
• 危险品标志：
  Xn
• 安全说明：
  S24,S37,S45
• 危险类别码：
  R42/43
• WGK Germany：
  2
• 海关编码：
  2941500000
• 危险品运输编号：
  NONH for all modes of transport

制备方法与用途

红霉素简介

红霉素（Erythromycin，EM，Er）是一种由红色链丝菌产生的碱性抗生素，属于大环内酯类窄谱抗菌素。主要包括红霉素A（Er A）、B（Er B）、C（Er C）、D（Er D）、E（Er E）和F（Er F）。其中游离碱适用于口服，乳糖酸盐可用于注射。红霉素常用于治疗对青霉素耐药的革兰氏阳性菌感染及对青霉素过敏的替代治疗。

临床应用

临床上常用红霉素来治疗对青霉素耐药的革兰氏阳性菌引起的感染以及青霉素过敏患者。它对于军团菌肺炎、支原体肺炎、沙眼衣原体导致的婴儿肺炎和结肠炎，皮肤软组织感染等是首选药物，并且适用于溶血性链球菌及肺炎球菌所致的呼吸道感染，尤其在白喉带菌者中与白喉抗毒素联用时能增强疗效。

作用机制

红霉素作为胃动素受体激动剂，其分子糖苷链上的二甲胺基团和14元内酯环的空间结构与胃动素相似。它可以诱发空腹状态下的第三相MMC收缩提前发生，从而引起胃、十二指肠平滑肌的收缩。低剂量红霉素可以促进自发性MMC的发生，而高剂量则会引起强烈不规则的胃肠道反应，导致呕吐，这也是其常见的胃肠道副作用。

用途

红霉素具有广泛的临床应用价值，能够有效治疗消化系统疾病。EM对全胃肠道均有不同程度的促动力作用，主要包括：增强食管收缩、提高下端括约肌的压力（LESP）；促进胃窦收缩及改善十二指肠功能协调性；诱导移行复合运动；促进结肠蠕动和胆囊收缩等。因此，它能够有效治疗各种消化系统疾病。

性状

红霉素是一种白色或类白色的结晶粉末，无臭、略带苦味，并具有一定的吸湿性。其化学性质呈弱碱性，在水中的溶解度较低（约0.2%），但易溶于有机溶剂。在酸性条件下不稳定。

抗菌作用

红霉素通过抑制细菌的蛋白合成发挥抗菌作用，主要用于革兰氏阳性菌感染治疗，尤其是对青霉素G耐药的金色葡萄球菌感染。它是大环内酯类抗生素中的一种常用药物，具有与青霉素相似的抗菌谱，适用于青霉素过敏患者或对青霉素耐药的金葡菌感染，同时也可用于链球菌、肺炎球菌感染及白喉带菌者的治疗。

生产方法

红霉素是由红色链丝菌（Streptomyces erythreus）发酵产生的碱性抗生素。其提取过程包括：利用该物质在不同酸碱度下溶解于不同溶剂的特性，采用乙酸丁酯和水溶液反复萃取以浓缩提纯，最后在乙酸丁酯中冷冻结晶获得红霉素碱。

反应信息

• 作为反应物：
  描述：

  红霉素 在 双氧水 作用下， 以 甲醇 为溶剂， 以88%的产率得到红霉素A氧化物
  参考文献：
  名称：

  使用MNBA进行大环内酯化在红霉素A糖苷配基合成中的效率评估

  摘要：

  在4-（二甲基氨基）吡啶（DMAP）存在下，使用2-甲基-6-硝基苯甲酸酐（MNBA）由相应的癸二酸制备各种合成红霉素A的糖苷的中间体。没有三乙胺。通过研究该方法并将结果与​​其他已建立的大环化方案的结果进行比较，可以评估MNBA内酯化的效率。最终得出结论：（i）在MNBA和DMAP存在的温和反应条件下，用于单体环化的构象合适的底物以优异的收率得到了所需的内酯；（ii）高度环化的底物也提供了所需的内酯。 （100）在甲苯中100°C时产率较高的单体内酯；以及（iii）具有稳定线性构象的癸二酸，与形成单体内酯相比，它更优选二聚，提供了高收率的相应乙交酯，且单体与二聚内酯的比例保持恒定（约1/5）。©2009日本化学杂志论坛和Wiley Periodicals，Inc.化学建议9：305–320；2009年：在线发布在Wiley InterScience（www.interscience.wiley

  DOI：

  10.1002/tcr.200900017
• 作为产物：
  描述：

  在 甲醇 、 N-氯代丁二酰亚胺 、 sodium amalgam 、 水 、 silver fluoride 作用下， 以 吡啶 、 六甲基磷酰三胺 为溶剂， 生成 红霉素
  参考文献：
  名称：

  红霉素的不对称全合成。3. 红霉素的全合成

  摘要：

  在之前的论文中，我们描述了光学活性形式的关键内酯中间体 1a 的制备。在本文中，我们报告了来自 la 的红霉素 (2) 的合成。从本质上讲，这种转化包括用 L-cladinose 和 D-desosamine 对 la 的合适衍生物进行糖苷化，并产生 C-9 酮官能团。

  DOI：

  10.1021/ja00401a051
• 作为试剂：
  描述：

  9-蒽甲醛 在 sodium hydride 、 二异丁基氢化铝 、 红霉素 作用下， 以 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (E)-3-(anthracen-9-yl)prop-2-en-1-ol
  参考文献：
  名称：

  Wavelength Dependent Trans to Cis and Quantum Chain Isomerizations of Anthrylethylene Derivatives

  摘要：

  Anthrylethylene derivatives 1-4 were synthesized to study their photoisomerization. Interestingly 1 and 2 displayed wavelength dependent trans to cis photoisomerization, whose origin is due to preferential light absorption and excitation of the trans isomer. Triplet sensitization studies revealed that these anthrylethylenes undergo only cis to trans isomerization and not trans to cis isomerization. UV-vis absorption, fluorescence emission, and fluorescence quantum yields were determined for all anthrylethylenes. Dual fluorescence is observed for 1, 2, and cis-1, indicating two different emissive states. The fluorescence solvatochromism displayed by 1, 2, and cis-1 is a clear indication of the involvement of a charge transfer excited state. The quantum yield of isomerization was determined in various solvents and also as a function of concentration. We report here the first ''quantum chain isomerization'' that originates from a singlet excited state. The rationale put forward for the observed quantum chain isomerization process is the involvement of adiabatic isomerization from the singlet excited state and subsequent energy transfer to a ground state molecule.

  DOI：

  10.1021/jo00129a043

文献信息

• Additives and products including oligoesters
  申请人：——

  公开号：US20030199593A1

  公开（公告）日：2003-10-23

  The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.

  本发明涉及寡酯及其用途或添加剂的制备。含有寡酯的添加剂和/或寡酯本身可用于配制药物制剂、化妆品或个人护理产品，如洗发水和护发素。这些寡酯对于制备能够赋予调理、长效性和/或紫外线保护的多功能添加剂特别有用。描述了单独的寡酯和寡酯混合物。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [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。
• [EN] ANTIBACTERIAL 8-PHENYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS ANTIBACTÉRIENS DE 8-PHÉNYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021219578A1

  公开（公告）日：2021-11-04

  The invention provides novel imidazopyrazine derivatives having the general formula (I), wherein X and R3 to R9 are as described herein or pharmaceutically acceptable salts thereof, wherein X and R3 to R9 are as defined herein. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.

  这项发明提供了具有一般式(I)的新型咪唑吡嗪衍生物，其中X和R3至R9如本文所述或其药学上可接受的盐，其中X和R3至R9如本文所定义。还提供了包括这些化合物的药物组合物、制造这些化合物的方法以及将这些化合物用作药物的方法，特别是将这些化合物用作抗生素治疗或预防细菌感染及由此导致的疾病的方法。