4-O-[(2R,3S,4R,6S)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-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-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] 1-O-ethyl butanedioate | 1264-62-6

• 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
• 英文名称: 4-O-[(2R,3S,4R,6S)-4-(dimethylamino)-2-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-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-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] 1-O-ethyl butanedioate
• CAS: 1264-62-6
• 化学式: C₄₃H₇₅NO₁₆
• 分子量: 862.1
• InChiKey: NSYZCCDSJNWWJL-HEESAXMSSA-N

物化性质

• 熔点：
  219-224 C
• 沸点：
  778.19°C (rough estimate)
• 密度：
  1.1417 (rough estimate)
• 闪点：
  >110°(230°F)
• 溶解度：
  乙醇：可溶50mg/mL
• 颜色/状态：
  WHITE OR SLIGHTLY YELLOW, CRYSTALLINE POWDER
• 气味：
  ODORLESS OR PRACTICALLY SO
• 味道：
  PRACTICALLY TASTELESS
• 稳定性/保质期：
  AFTER RECONSTITUTION OF COMMERCIALLY AVAILABLE POWDER, SUSPENSIONS ARE STABLE FOR 10 DAYS @ 2-8 °C
• 折光率：
  INDEX OF REFRACTION: 1.490 (ALPHA), 1.515 (BETA), 1.567 (GAMMA)
• 解离常数：
  PKA 7.1

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  60
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  226
• 氢给体数：
  4
• 氢受体数：
  17

ADMET

毒理性

• 人类毒性摘录

在超敏反应中包括发热、嗜酸性粒细胞增多和皮肤疹，每一种都可能出现单独或联合；停止治疗不久后它们就会消失。...可能会产生刺激性影响。口服给药...常伴有上腹部不适，这可能非常严重。/红霉素/

AMONG HYPERSENSITIVITY REACTIONS ARE FEVER, EOSINOPHILIA, & SKIN ERUPTIONS, EACH OF WHICH MAY OCCUR ALONE OR IN COMBINATION; THEY DISAPPEAR SHORTLY AFTER THERAPY IS STOPPED. ...MAY PRODUCE IRRITATIVE EFFECTS. ORAL ADMIN...FREQUENTLY ACCOMPANIED BY EPIGASTRIC DISTRESS, WHICH MAY BE QUITE SEVERE. /ERYTHROMYCIN/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

静脉注射超过100毫克的剂量会产生...严重疼痛...持续数小时；静脉输注1克剂量...几乎经常会导致血栓性静脉炎。 ...6名患者...在以4克/天...静脉给药治疗期间出现了听力困难。 ...停止治疗后...听力完全恢复正常... /红霉素/

IM INJECTION OF QUANTITIES LARGER THAN 100 MG PRODUCES...SEVERE PAIN... PERSISTS FOR HR: IV PERFUSIONS OF 1-G DOSES...ALMOST REGULARLY IS FOLLOWED BY THROMBOPHLEBITIS. ...6 PT...DEVELOPED DIFFICULTY IN HEARING WHILE BEING TREATED WITH 4 G/DAY...IV. ... CESSATION...LED TO COMPLETE RETURN OF NORMAL HEARING... /ERYTHROMYCIN/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

一个60岁女性因使用红霉素乙基琥珀酸酯治疗导致肝毒性的病例报告。

A CASE REPORT OF HEPATOTOXICITY RESULTING FROM ERYTHROMYCIN ETHYLSUCCINATE THERAPY IN 60-YR-OLD FEMALE IS DESCIRBED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

红霉素琥乙酯在肠道中部分解离；红霉素和未解离的酯都能被吸收，在血液中，酯被水解以释放游离的红霉素。

ERYTHROMYCIN ETHYLSUCCINATE IS PARTIALLY DISSOCIATED IN INTESTINE; BOTH ERYTHROMYCIN & UNDISSOCIATED ESTER ARE ABSORBED &, IN THE BLOOD, THE ESTER IS HYDROLYZED TO RELEASE FREE ERYTHROMYCIN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

红霉素琥乙酯...在口服给药后能够充分吸收，尤其是当胃部为空时。在服用500毫克片剂后1到2小时内，血浆中的峰浓度达到1.5微克/毫升（0.5微克/毫升的碱基）。

ERYTHROMYCIN ETHYLSUCCINATE...IS ADEQUATELY ABSORBED FOLLOWING ORAL ADMINISTRATION, PARTICULARLY WHEN THE STOMACH IS EMPTY. PEAK CONCENTRATIONS IN PLASMA ARE 1.5 UG/ML (0.5 UG/ML OF BASE) 1 TO 2 HR AFTER ADMINISTRATION OF A 500 MG TABLET.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在患者中，红霉素的平均胆汁水平大约是静脉注射（红霉素乳糖酸盐）和肌肉注射（红霉素琥珀酸酯）1小时后相应血清浓度的10倍。

IN PATIENTS, MEAN BILE LEVELS OF ERYTHROMYCIN WERE APPROXIMATELY 10 TIMES HIGHER THAN CORRESPONDING SERUM CONCN 1 HR AFTER IV (ERYTHROMYCIN LACTOBIONATE) & IM (ERYTHROMYCIN SUCCINATE) INJECTION.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在健康的成年受试者和患有支气管感染的成年患者中，研究了不同剂型的红霉素的药代动力学。红霉素琥乙酯比红霉素硬脂酸盐更适合口服治疗，因为它能快速且一致地被吸收。

IN HEALTHY ADULT SUBJECTS & IN ADULT PATIENTS WITH BRONCHIAL INFECTIONS, PHARMACOKINETICS OF VARIOUS FORMULATIONS OF ERYTHROMYCIN WERE STUDIED. ERYTHROMYCIN ETHYLSUCCINATE WAS BETTER THAN ERYTHROMYCIN STEARATE FOR ORAL TREATMENT IN THAT IT WAS RAPIDLY & CONSISTENTLY ABSORBED.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 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
• RTECS号：
  WM9800000

制备方法与用途

生物活性

Erythromycin Ethylsuccinate 是一种口服的大环内酯类抗菌素，由链霉菌产生。它可以可逆地结合细菌50S核糖体并抑制蛋白合成。

体外研究

Erythromycin 对金黄色葡萄球菌、肺炎链球菌、化脓性链球菌、流感嗜血杆菌、卡他莫拉菌、百日咳杆菌、淋球菌、空肠弯曲杆菌、幽门螺旋杆菌和伯氏疏螺旋体均具有抗菌活性。此外，Erythromycin 还是一种胃动素受体激动剂，它作为胃肠道肌动活性的有效激动剂发挥作用。

在体外研究中，Erythromycin 引导对超大剂量乙酰胆碱产生50%的最大收缩响应所需的浓度为2 μM。取代50%标记的胃动素所需浓度为13 μM。值得注意的是，Erythromycin 对大鼠或狗十二指肠的肌条没有作用，但在人体肌肉条中诱导了收缩。

化学性质

白色结晶性粉末。

用途

Erythromycin 属于抗生素类药物，主要用于治疗青霉素耐药的葡萄球菌感染。

文献信息

• 8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents
  申请人：Bradbury J. Barton

  公开号：US20060173026A1

  公开（公告）日：2006-08-03

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , A 8 , R 2 , R 3 , R 5 , R 6 , R 7 , and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of compounds of Formula I and/or Formula II and one or more other active agents. The invention also provides methods for treating microbial and protozoal infections in animals.

  该发明提供了具有抗微生物活性的化合物和盐，其化学结构分别为公式I和公式II。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。变量A1，A8，R2，R3，R5，R6，R7和R9在此处有定义。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和选择性抑制剂。该发明还提供了包含公式I或公式II化合物以及一个或多个载体、赋形剂或稀释剂的抗微生物组合物，包括制药组合物。这些组合物可以含有公式I或公式II化合物作为唯一活性剂，也可以含有公式I和/或公式II化合物以及一个或多个其他活性剂的组合。该发明还提供了治疗动物微生物和原虫感染的方法。
• [EN] MODULATION OF IMMUNE RESPONSES BY ADMINISTRATION OF ROXITHROMYCIN OR ITS DERIVATIVE<br/>[FR] MODULATION DES RÉPONSES IMMUNES PAR ADMINISTRATION DE ROXITHROMYCINE OU DE SES DÉRIVÉS
  申请人：Y S THERAPEUTICS CO LTD

  公开号：WO2009023196A1

  公开（公告）日：2009-02-19

  Provided are compounds of formula (III) useful for modulation of immune responses, compositions comprising the compounds, and methods of use of such compositions for treating diseases or disorders involving an immune response. In certain embodiments, the compounds are useful for the treatment of diseases or disorders associated with transendothelial migration of T cells and activated T cells, and proinflammatory cytokine production from T cells and macrophages. Diseases or disorders that can be treated include arthritic and rheumatic disorders, such as rheumatoid arthritis.

  提供的是化合物的公式（III），用于调节免疫反应，包含这些化合物的组合物，以及使用这些组合物治疗涉及免疫反应的疾病或紊乱的方法。在某些实施例中，这些化合物可用于治疗与T细胞和活化T细胞的经内皮迁移以及T细胞和巨噬细胞的促炎细胞因子产生相关的疾病或紊乱。可以治疗的疾病或紊乱包括关节炎和风湿性疾病，如类风湿性关节炎。
• 8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents
  申请人：Bradbury J. Barton

  公开号：US20060100215A1

  公开（公告）日：2006-05-11

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables n, m, p, R A , R B , A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and/or selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in eukaryotes.

  该发明提供了化合物和盐的公式I和公式II：具有抗微生物活性。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。这里定义了变量n、m、p、RA、RB、A1、R2、R3、R5、R6、R7、A8和R9。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和/或选择性抑制剂。该发明还提供了抗微生物组合物，包括含有一个或多个公式I或公式II化合物和一个或多个载体、赋形剂或稀释剂的制药组合物。这些组合物可能仅含有公式I或公式II化合物作为唯一活性剂，也可能含有公式I或公式II化合物与一个或多个其他活性剂的组合。该发明还提供了治疗真核生物微生物感染的方法。
• 2-SUBSTITUTED-THIENOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
  申请人：Phadke Avinash

  公开号：US20130165471A1

  公开（公告）日：2013-06-27

  Disclosed herein are 2-substituted-thienoquinolones and related compounds and their pharmaceutically acceptable salts useful as antiviral agents and having the general formula in which the variables R 2 , R 3 , and R 7 are defined herein. Certain compounds provided herein possess potent antibacterial, antiprotozoal, or antifungal activity and are particularly efficacious for the treatment of MRSA infections. The invention also provides pharmaceutical compositions, pharmaceutical compositions containing a 2-substituted-thienoquinolone in combination with one or more other active agent, and methods of treating microbial infections in animals by administering an effective amount of a 2-substituted-thienoquinolone to an animal suffering from a microbial infection.

  本文公开了2-取代噻吩喹啉及相关化合物和其药学上可接受的盐，作为抗病毒剂，并具有以下一般式中定义的变量R2，R3和R7。本文提供的某些化合物具有强大的抗菌、抗原虫或抗真菌活性，特别适用于治疗MRSA感染。本发明还提供了制药组合物，其中包含2-取代噻吩喹啉与一种或多种其他活性剂的组合物，以及通过向患有微生物感染的动物施用有效量的2-取代噻吩喹啉来治疗动物的微生物感染的方法。
• HYDROXYTHIENOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
  申请人：BRADBURY Barton James

  公开号：US20100256112A1

  公开（公告）日：2010-10-07

  Disclosed herein are hydroxylthienoquinolones and related compounds and their pharmaceutically acceptable salts useful as antiviral agents and having the general formula in which the variables R 2 , R 6 , and R 7 are defined herein. Certain compounds provided herein possess potent antibacterial, antiprotozoal, or antifungal activity and are particularly efficacious for the treatment of MRSA infections. The invention also provides pharmaceutical compositions, pharmaceutical compositions containing a hydroxylthienoquinolone in combination with one or more other active agent, and methods of treating microbial infections in animals by administering an effective amount of a hydroxylthienoquinolone or related compound to an animal suffering from a microbial infection.

  本文披露了羟基噻唑喹啉和相关化合物及其药学上可接受的盐，可用作抗病毒剂，并具有以下通用式的R2、R6和R7变量的定义。本文提供的某些化合物具有强大的抗菌、抗原虫或抗真菌活性，并特别适用于治疗MRSA感染。本发明还提供了制药组合物、含有羟基噻唑喹啉与一种或多种其他活性剂的制药组合物，以及通过向患有微生物感染的动物投予有效量的羟基噻唑喹啉或相关化合物来治疗动物的微生物感染的方法。