clarithromycin

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: clarithromycin
• 英文别名: (3R,4S,5S,6R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• 化学式: C₃₈H₆₉NO₁₃
• 分子量: 747.965
• InChiKey: AGOYDEPGAOXOCK-MQDHJOFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  52
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  183
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  clarithromycin 在 盐酸 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 水 、 戴斯-马丁氧化剂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 19.16h， 生成
  参考文献：
  名称：

  [EN] CONVERGENT PROCESSES FOR PREPARING MACROLIDE ANTIBACTERIAL AGENTS
  [FR] PROCÉDÉS CONVERGENTS DE PRÉPARATION D'AGENTS ANTIBACTÉRIENS MACROLIDES

  摘要：

  本发明涉及制备酮酸类抗菌剂的过程。特别是，本发明涉及中间体和制备酮酸类化合物的过程，其中包括1,2,3-三唑取代的侧链。

  公开号：

  WO2014145210A1

文献信息

• Novel Clarithromycin Analogs with C-4” 2-arylbenzimidazolyl Bishydrazide Side Chain: Synthesis and Antibacterial Evaluation
  作者：Yunkun Qi、Ruixin Ma、Xin Li、Yue Hu、Siti Ma、Chao Cong、Xiaodong Ma、Wenping Cui、Shutao Ma

  DOI：10.2174/157018011797655269

  日期：2011.12.1

  A series of novel 4” -O-2-arylbenzimidazolyl derivatives of clarithromycin were synthesized and evaluated. These 4” -O-2-arylbenzimidazolyl derivatives demonstrated excellent activity against erythromycin-susceptible strains and showed remarkably improved activity against erythromycin-resistant strains compared with the references. In particular, compound 7c, which possesses the terminal 2-(2-methoxyphenyl)benzimidazolyl group on the C-4” bishydrazide side chain, not only presented the most potent activity against erythromycin-susceptible Streptococcus pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923, exhibiting 4-fold and 4-fold higher efficacy than the parent clarithromycin, but also displayed the highest activity against erythromycin-resistant Streptococcus pneumoniae expressing the mef gene and the erm gene, which was 133-fold and 32-fold better than clarithromycin or azithromycin, respectively.

  一系列新型的克拉霉素4”-O-2-芳基苯并咪唑衍生物被合成并评估。这些4”-O-2-芳基苯并咪唑衍生物对红霉素敏感菌株显示出优异的活性，并且相较于参考药物，对红霉素耐药菌株的活性显著提高。特别是化合物7c，其在C-4”双酰肼侧链上带有末端的2-（2-甲氧基苯基）苯并咪唑基团，不仅对红霉素敏感的肺炎链球菌ATCC49619和金黄色葡萄球菌ATCC25923表现出最强的活性，效能分别是母体克拉霉素的4倍和4倍，而且对表达mef基因和erm基因的红霉素耐药肺炎链球菌的活性也是最高的，分别是克拉霉素或阿奇霉素的133倍和32倍。
• Design, synthesis and antibacterial activity of novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain
  作者：Qiu-Ling Song、Bao-Qin Guo、Wen Zhang、Ping Lan、Ping-Hua Sun、Wei-Min Chen

  DOI：10.1038/ja.2011.50

  日期：2011.8

  A set of 17 novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain were synthesized and evaluated for their antibacterial activities, which the aryltetrazolyl group was selected to replace the hetero-aryl moiety of the side chain in telithromycin for designing new compounds. The synthesis of aryltetrazolyl alkylamines was reported in detail. The antibacterial activities of new ketolides were evaluated against a number of pathogens including macrolide-resistant organisms by using telithromycin as the reference. Many of the evaluated compounds exhibited remarkable activities against both erythromycin-susceptible and erythromycin-resistant organisms such as Staphylococcus aureus (except S. aureus AD-08), Pseudomonas aeruginosa and Escherichia coli. Among these, the compound 11e exhibited excellent antibacterial potency against all the strains in comparison with others.

  合成了一组17种新型酮类抗生素，具有取代芳基四氮唑的烷基侧链，并评估了它们的抗菌活性。芳基四氮唑基团的选择是为了替代泰利霉素侧链中的杂芳基，旨在设计新的化合物。详细报告了芳基四氮唑烷基胺的合成过程。新型酮类抗生素的抗菌活性是针对包括大环内酯耐药菌在内的多种病原体进行评估，使用泰利霉素作为参考。许多评估的化合物对包括金黄色葡萄球菌（除了 S. aureus AD-08）、绿脓杆菌和大肠杆菌在内的红霉素敏感菌和红霉素耐药菌表现出显著的抗菌活性。在这些化合物中，化合物11e与其他化合物相比，显示出对所有菌株的极佳抗菌效能。
• Synthesis and Antibacterial Activity of Novel 4″-<i>O</i>-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains
  作者：Zhe-Hui Zhao、Di Zhu、Xiao-Xi Zhang、Zhi-Gang Luo、Ping-Sheng Lei

  DOI：10.1080/10286020.2018.1462341

  日期：2019.7.3

  A series of novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors (18, 19) with 4″-OH of compounds 5a–c. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and

  一系列新颖的4 - “ ø 11，12 -芳基烷基侧链-desosaminyl克拉霉素衍生物是通过偶合-6-脱氧-德糖胺供体（合成18，19的化合物与-OH 4）”图5a - Ç。针对一系列对大环内酯敏感和大环内酯耐药的病原体测试了目标化合物的活性。它们中的一些显示出对大环内酯敏感和抗性病原体的活性，化合物21d和21e显示出对抗药性病原体的活性的显着改善。
• Synthesis and antibacterial activity of 4″-O-carbamoyl analogs of clarithromycin
  作者：Xue Cui Shen、Bo Jiao、Shu Tao Ma

  DOI：10.1016/j.cclet.2009.11.023

  日期：2010.3

  Abstract A series of novel 4″- O -carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S. pneumoniae . Particularly, 4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene, and remarkably

  摘要合成了一系列新颖的克拉霉素4” -O-氨基甲酰基类似物，并对其体外抗菌活性进行了评价。所有所需化合物均显示出对易患红霉素的肺炎链球菌的优异活性。特别地，4-氟苄基氨基甲酸酯7a显示出对由mef基因编码的抗红霉素的肺炎链球菌的有效活性，并显着提高了对由erm基因以及erm和mef基因编码的抗红霉素的肺炎链球菌的活性。
• Method for demethylating the 3'-dimethylamino group of erythromycin compounds
  申请人：Liu Yaoquan

  公开号：US20070135362A1

  公开（公告）日：2007-06-14

  A method for demethylating the 3′-dimethylamino group of erythromycin compounds.