3-[10-(4-Dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-ethyl-3,4-dihydroxy-9-methoxy-3,5,7,9,11,13-hexamethyl-12,14-dioxo-oxacyclotetradec-6-ylideneaminooxy]-piperidine-1-carboxylic acid benzyl ester | 143354-04-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[10-(4-Dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-ethyl-3,4-dihydroxy-9-methoxy-3,5,7,9,11,13-hexamethyl-12,14-dioxo-oxacyclotetradec-6-ylideneaminooxy]-piperidine-1-carboxylic acid benzyl ester
• 英文别名: benzyl 3-[(E)-[(2R,3S,4R,5S,7R,9R,10R,11R,13R)-10-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4-dihydroxy-9-methoxy-3,5,7,9,11,13-hexamethyl-12,14-dioxo-oxacyclotetradec-6-ylidene]amino]oxypiperidine-1-carboxylate
• CAS: 143354-04-5
• 化学式: C₄₃H₆₉N₃O₁₂
• 分子量: 820.034
• InChiKey: XTIPFGOWKMAPRC-SPKAJNPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  58
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  186
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  3-[10-(4-Dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-ethyl-3,4-dihydroxy-9-methoxy-3,5,7,9,11,13-hexamethyl-12,14-dioxo-oxacyclotetradec-6-ylideneaminooxy]-piperidine-1-carboxylic acid benzyl ester 在 palladium on activated charcoal 甲酸 、 氢气 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 16.0h， 生成 (3R,5R,6R,7R,9R,10E,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-10-[(3R)-1-methylpiperidin-3-yl]oxyimino-oxacyclotetradecane-2,4-dione
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

  摘要：

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

  DOI：

  10.1021/jm980240d
• 作为产物：
  描述：

  克拉霉素 在 盐酸 、 甲醇 、 三氟乙酸吡啶 、 potassium carbonate 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 59.0h， 生成 3-[10-(4-Dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-ethyl-3,4-dihydroxy-9-methoxy-3,5,7,9,11,13-hexamethyl-12,14-dioxo-oxacyclotetradec-6-ylideneaminooxy]-piperidine-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

  摘要：

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

  DOI：

  10.1021/jm980240d

文献信息

• Synthesis and Antibacterial Activity of Ketolides (6-<i>O</i>-Methyl-3-oxoerythromycin Derivatives):  A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens
  作者：Constantin Agouridas、Alexis Denis、Jean-Michel Auger、Yannick Benedetti、Alain Bonnefoy、François Bretin、Jean-François Chantot、Arlette Dussarat、Claude Fromentin、Solange Gouin D'Ambrières、Sylvette Lachaud、Patrick Laurin、Odile Le Martret、Véronique Loyau、Nicole Tessot

  DOI：10.1021/jm980240d

  日期：1998.10.1

  In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11,12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLS(B) resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.