2'-O-acetyl-4''-O-acylimidazolylclarithromycin | 869358-00-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-acetyl-4''-O-acylimidazolylclarithromycin
• 英文别名: 2'-O-acetyl-4"-O-acylimidazolylclarithromycin；2'-O-acetyl-4"-O-(1-imidazolyl-carbonyl)-6-O-methyl-erythromycin A；[(2S,3S,4R,6R)-6-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-3-acetyloxy-4-(dimethylamino)-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-4-yl]oxy]-4-methoxy-2,4-dimethyloxan-3-yl] imidazole-1-carboxylate
• CAS: 869358-00-9
• 化学式: C₄₄H₇₃N₃O₁₅
• 分子量: 884.075
• InChiKey: LYGSJNPASMMHOC-FWWBCVFZSA-N

物化性质

• 熔点：
  147-150 °C
• 沸点：
  876.3±75.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  62
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  213
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  2'-O-acetyl-4''-O-acylimidazolylclarithromycin 在 甲醇 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 4"-O-(3,4-methylenedioxyphenethyl)carbamoylclarithromycin
  参考文献：
  名称：

  Synthesis and antibacterial evaluation of novel clarithromycin derivatives with C-4″ elongated arylalkyl groups against macrolide-resistant strains

  摘要：

  Novel clarithromycin derivatives with C-4 '' elongated arylalkyl groups were designed, synthesized and evaluated to probe the effect of different lengths of their C-4 '' side chains on the activity against resistant bacterial strains. These derivatives had excellent activity against erythromycin-susceptible Streptococcus pneumoniae, Streptococcus aureus or Streptococcus pyogenes and some of them exhibited greatly improved activity against erythromycin-resistant strains. Compounds 18 and 16, which had the C-4 '' elongated arylalkyl groups with eight atoms from the 4 ''-oxygen atom to the terminal benzene ring, were the most effective against S. pneumoniae expressing the erm gene and the erm and me! genes. In contrast, the most potent compounds 3, 5, 9,17 and 18 against S. pneumoniae expressing the mef gene had C-4 '' elongated arylalkyl groups with three to eight atoms between the 4 ''-oxygen atom and the terminal aromatic ring. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.035
• 作为产物：
  描述：

  克拉霉素 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 2'-O-acetyl-4''-O-acylimidazolylclarithromycin
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of BODIPY®–erythromycin probes for bacterial ribosomes

  摘要：

  BODIPY (R)-erythromycin probes of bacterial ribosomes were designed and synthesized by attaching a BODIPY (R) fluorophore to the 4"- and 9-positions of the erythromycin structure. The probes exhibited excellent binding affinity to bacterial ribosomes and competed with erythromycin and other drugs whose binding sites are in the same vicinity of the 50S subunit. The synthetic fluorescent probe 5 was successfully adapted in our ultra high-throughput screening (uHTS) to identify novel ribosome inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.11.028

文献信息

• [EN] CARBAMATE LINKED MACROLIDES USEFUL FOR THE TREATMENT OF MICROBIAL INFECTIONS<br/>[FR] MACROLIDES A LIAISON CARBAMATE UTILISES DANS LE TRAITEMENT DES INFECTIONS MICROBIENNES
  申请人：PLIVA ISTRAZIVACKI INST D O O

  公开号：WO2005108413A1

  公开（公告）日：2005-11-17

  The present invention relates to 14- or 15-membered macrolides substituted at the 4' position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical microbial infections in a human or animal body.

  本发明涉及在式(I)的4'位置被取代的14-或15-元大环内酯及其药学上可接受的衍生物，以及它们的制备过程和在人体或动物体内治疗或预防全身或局部微生物感染中的用途。
• Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives
  作者：Chao Cong、Haiyang Wang、Yue Hu、Chen Liu、Siti Ma、Xin Li、Jichao Cao、Shutao Ma

  DOI：10.1016/j.ejmech.2011.04.004

  日期：2011.7

  Novel 4 ''-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These benzimidazolyl derivatives exhibited excellent activity against erythromycin-susceptible strains better than the references, and some of them showed greatly improved activity against erythromycin-resistant strains. Compounds 16 and 17, which have the terminal 2-(4-methylphenyl)benzimidazolyl and 2-(2-methoxyphenyl)benzimidazolyl groups on the C-4 '' bishydrazide side chains, were the most active against erythromycin-resistant Staphylococcus pneumoniae expressing the erm gene and the me! gene. In addition, compound 17 exhibited the highest activity against erythromycin-susceptible S. pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923 as well. It is worth noting that the 4 ''-O-(2-aryl)benzimidazolyl derivatives show higher activity against erythromycin-susceptible and erythromycin-resistant strains than the 4 ''-O-(2-alkyl) benzimidazolyl derivatives. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis and antibacterial activity of novel 4″-O-arylalkylcarbamoyl and 4″-O-((arylalkylamino)-4-oxo-butyl)carbamoyl clarithromycin derivatives
  作者：Yongjing Ju、Ruiqing Xian、Ling Zhang、Ruixin Ma、Jichao Cao、Shutao Ma

  DOI：10.1016/j.bmcl.2010.04.051

  日期：2010.6

  Novel series of novel 4 ''-O-arylalkylcarbamoyl and 4 ''-O-((arylalkylamino)-4-oxo-butyl) carbamoyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These derivatives retained excellent activity against the erythromycin-susceptible strains and showed significantly improved activity against all of the tested erythromycin-resistant strains. Among them, compound 4c was the most effective (0.06 mu g/mL) against Streptococcus pneumonia encoded by the erm gene and compound 4a was had the most potent activity (0.25 mu g/mL) against S. pneumonia encoded by the erm and mef genes. (C) 2010 Elsevier Ltd. All rights reserved.
• Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin
  作者：Gennady B. Lapa、Elena P. Mirchink、Elena B Isakova、Maria N Preobrazhenskaya

  DOI：10.1080/14756366.2016.1261129

  日期：2017.1.1

  Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2] oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 400 position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone's cycle via oxime linker, the second direction used the modification of the 400-O-group of cladinose via the formation of carbamates of benzoxaboroles. 4''-O-(3-S-(1-Hydroxy-1,3-dihydro-benzo[c][1,2] oxaborole)-methyl-carbamoyl-clarithromycin showed twofold decrease in MICs for S. epidermidis and S. pneumoniae than clarithromycin. 4''-O-Modified clarithromycin demonstrated an efficacy against Gram positive strains only. Compounds with C-9 substitution were more active than 4''-O-substituted antibiotics for susceptible strains E. coli tolC and did not exceed the activity of initial antibiotics.