(3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[4-(Dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-(5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl)oxy-10-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one | 80214-83-1

• 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: (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[4-(Dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-(5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl)oxy-10-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
• CAS: 80214-83-1
• 化学式: C₄₁H₇₆N₂O₁₅
• 分子量: 837.0
• InChiKey: RXZBMPWDPOLZGW-KMAKEOJNSA-N

物化性质

• 熔点：
  111-118?C
• 比旋光度：
  D25 -77.5 ±2° (c = 0.45 in chloroform)
• 沸点：
  864.7±75.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)
• 闪点：
  >110°(230°F)
• 溶解度：
  氯仿：可溶,10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  58
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  217
• 氢给体数：
  5
• 氢受体数：
  17

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：罗红霉素在美国未获得食品药品监督管理局的市场批准，但在其他国家可用。由于母乳中罗红霉素含量较低，预计不会对哺乳婴儿造成不良影响。监测婴儿可能出现的影响胃肠道菌群的情况，如腹泻、念珠菌病（鹅口疮、尿布疹）。未经证实的流行病学证据表明，在母乳喂养的前两周内，母亲使用大环内酯类抗生素可能会增加婴儿肥厚性幽门狭窄的风险，但也有人对此关系表示质疑。 ◉ 对哺乳婴儿的影响：一项对诊断为婴儿肥厚性幽门狭窄的婴儿队列研究发现，受影响的婴儿在分娩后90天内母亲使用大环内酯类抗生素的可能性是正常婴儿的2.3到3倍。对婴儿进行分层后发现，女性婴儿的比值比为10，男性婴儿为2。所有受影响婴儿的母亲都哺乳了她们的婴儿。大多数大环内酯类药物的处方是红霉素，但19%是罗红霉素。然而，作者没有说明受影响婴儿的母亲使用了哪种大环内酯类药物。 一项在丹麦进行的15年数据回顾性数据库研究发现，在分娩后前13天内使用大环内酯类药物的母亲所生婴儿患婴儿肥厚性幽门狭窄的风险增加了3.5倍，但后期暴露没有发现这种风险。不知道有多少婴儿被母乳喂养，但可能比例很高。也没有报告使用每种大环内酯类药物的妇女比例。 一项比较了母亲使用阿莫西林和母亲使用大环内酯类抗生素的哺乳婴儿的研究发现，没有一例婴儿出现幽门狭窄。在通过母乳接触大环内酯类药物的婴儿中，有67%接触了罗红霉素。在接触大环内酯类药物的婴儿中，有12.7%出现了不良反应，这与接触阿莫西林的婴儿的不良反应率相似。反应包括皮疹、腹泻、食欲不振和嗜睡。 两项荟萃分析未能证明母亲在哺乳期间使用大环内酯类药物与婴儿肥厚性幽门狭窄之间存在关系。 ◉ 对泌乳和母乳的影响：在冈比亚进行的一项双盲对照研究中，给鼻咽部携带金黄色葡萄球菌、肺炎链球菌或B族链球菌的妇女在分娩时单次给予2克阿奇霉素。接受阿奇霉素的妇女的乳汁样本中病原体的携带率为9.6%，而接受安慰剂的妇女为21.9%。母亲和婴儿在分娩后第6天的鼻咽部携带率也有所降低。

◉ Summary of Use during Lactation:Roxithromycin is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Because of the low levels of roxithromycin in breastmilk, it would not be expected to cause adverse effects in breastfed infants. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash). Unconfirmed epidemiologic evidence indicates that the risk of infantile hypertrophic pyloric stenosis might be increased by maternal use of macrolide antibiotics during the first two weeks of breastfeeding, but others have questioned this relationship. ◉ Effects in Breastfed Infants:A cohort study of infants diagnosed with infantile hypertrophic pyloric stenosis found that affected infants were 2.3 to 3 times more likely to have a mother taking a macrolide antibiotic during the 90 days after delivery. Stratification of the infants found the odds ratio to be 10 for female infants and 2 for male infants. All of the mothers of affected infants nursed their infants. Most of the macrolide prescriptions were for erythromycin, but 19% were for roxithromycin. However, the authors did not state which macrolide was taken by the mothers of the affected infants. A retrospective database study in Denmark of 15 years of data found a 3.5-fold increased risk of infantile hypertrophic pyloric stenosis in the infants of mothers who took a macrolide during the first 13 days postpartum, but not with later exposure. The proportion of infants who were breastfed was not known, but probably high. The proportion of women who took each macrolide was also not reported. A study comparing the breastfed infants of mothers taking amoxicillin to those taking a macrolide antibiotic found no instances of pyloric stenosis. Sixty-seven percent of the infants exposed to a macrolide in breastmilk were exposed to roxithromycin. Adverse reactions occurred in 12.7% of the infants exposed to macrolides which was similar to the rate in amoxicillin-exposed infants. Reactions included rash, diarrhea, loss of appetite, and somnolence. Two meta-analyses failed to demonstrate a relationship between maternal macrolide use during breastfeeding and infantile hypertrophic pyloric stenosis. ◉ Effects on Lactation and Breastmilk:In a double-blind, controlled study in Gambia, women who were nasopharyngeal carriers of Staphylococcus aureus, Streptococcus pneumoniae or group B streptococcus were given a single 2 gram dose of azithromycin during labor. Milk samples from women who received azithromycin had 9.6% prevalence of carriage of the organisms compared to 21.9% in women who received placebo. Nasopharyngeal carriage in mothers and infants was also reduced on day 6 postpartum.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2941500000
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  KF4990000

制备方法与用途

罗红霉素简介

罗红霉素是最常用的广谱高效消炎药之一，属于广谱抗菌药物。其常见剂型包括罗红霉素胶囊、肠溶片、分散片和干混悬剂等。该药常用于治疗化脓性链球菌引起的咽炎及扁桃体炎，以及其他由敏感细菌引起的各种炎症。

药理作用

罗红霉素是一种半合成的14元环大环内酯类抗生素，其作用机制与红霉素类似但更为强大，对革兰阳性菌的作用较红霉素略差，对嗜肺军团菌的作用较强。体外研究证实，罗红霉素对各种链球菌（包括A、B、C型链球菌和肺炎链球菌）、金黄色葡萄球菌（除MRSA外）、表皮葡萄球菌、嗜肺军团菌、杜克雷嗜血杆菌、沙眼衣原体、肺炎支原体及口腔或阴道厌氧菌的抗菌活性与红霉素几乎相同。卡他布兰汉球菌对罗红霉素高度敏感，对弯曲杆菌、百日咳杆菌、流感嗜血杆菌、结核杆菌和白喉杆菌也有抑制作用。

药代动力学

罗红霉素口服吸收良好，见效快。其生物利用度及血药浓度均高于红霉素。研究表明，单次口服150毫克后，血药峰浓度可达6.6～7.9微克/毫升，而同等条件下红霉素仅为0.2～0.4微克/毫升。

适应症

罗红霉素主要用于治疗呼吸道感染（如肺炎、急性支气管炎和慢性支气管炎的急性感染）、非典型肺炎、泌尿生殖系统感染及皮肤软组织感染。它对革兰氏阳性菌、厌氧菌、衣原体和支原体等有良好疗效，且不良反应较少。

注意事项

1. 本品与红霉素存在交叉耐药性。
2. 对本品过敏者禁用。
3. 不宜与麦角胺及二羟基麦角胺合用。

化学性质

罗红霉素为白色结晶性粉末，无臭味苦。易溶于乙醇或丙酮，较易溶于甲醇或乙醚，几乎不溶于水。其旋光度为[α]₂₃D-77.5°±2°（C=0.45，氯仿）。

生产方法

罗红霉素的生产以红霉素为原料，通过与盐酸羟胺在三乙胺和甲醇中反应生成肟，再与甲氧基乙氧基甲基氯在丙酮中反应获得。

文献信息

• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  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 A1, R2, R3, R5, R6, R7, A8 and R9 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 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 animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• 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。