5-O-desosaminyl-9-deoxo-9-dihydro-9a-[N'-(β-cyanoethyl)-N'-(1-naphthyl)carbamoyl-γ-aminopropyl]-9a-aza-9a-homoerythronolide A | 709653-30-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-desosaminyl-9-deoxo-9-dihydro-9a-[N'-(β-cyanoethyl)-N'-(1-naphthyl)carbamoyl-γ-aminopropyl]-9a-aza-9a-homoerythronolide A
• 英文别名: 1-(2-cyanoethyl)-1-[3-[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-oxo-1-oxa-6-azacyclopentadec-6-yl]propyl]-3-naphthalen-1-ylurea
• CAS: 709653-30-5
• 化学式: C₄₆H₇₃N₅O₁₀
• 分子量: 856.113
• InChiKey: HJFHVPCCOFNXRX-MXRSLKQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  61
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  阿奇霉素 A 在 盐酸 、 platinum on carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 60.0 ℃ 、400.01 kPa 条件下， 反应 60.0h， 生成 5-O-desosaminyl-9-deoxo-9-dihydro-9a-[N'-(β-cyanoethyl)-N'-(1-naphthyl)carbamoyl-γ-aminopropyl]-9a-aza-9a-homoerythronolide A
  参考文献：
  名称：

  Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae

  摘要：

  A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N '' substituted 9a-(N'-carbamoyl-gamma-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-gamma-aminopropyl)- (7a,e), 9a-[N'-(beta-cyanoethyl)-N'-(carbamoyl-gamma-aminopropyl)]- (9a-c, 9g) 9a-[N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-gamma-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.079

文献信息

• Novel ureas and thioureas of 15-membered azalides with antibacterial activity against key respiratory pathogens
  作者：Mirjana Bukvić Krajačić、Predrag Novak、Miljenko Dumić、Mario Cindrić、Hana Čipčić Paljetak、Nedjeljko Kujundžić

  DOI：10.1016/j.ejmech.2009.02.001

  日期：2009.9

  The new ureas and thioureas of 15-membered azalides, N ''-substituted 9a-(N'-carbamoyl-gamma-aminopropyl) (4), 9a-(N'-thiocarbamoyl-gamma-aminopropyl) (6), 9a-[N'-(beta-cyanoethyl)-N'-(carbamoyl-gamma-aminopropyl)] (8) and 9a-[N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-gamma-aminopropyl)] (10) of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2), were synthesized and structurally characterized by NMR and IR spectroscopic methods and mass spectrometry. The new compounds were evaluated in vitro against a panel of erythromycin susceptible and erythromycin-resistant Gram-positive and Gram-negative bacterial strains. These compounds displayed an excellent overall antibacterial in vitro activity against erythromycin sensitive Gram-positive strains, Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and good against negative strains, Moraxella catarrhalis and Haemophilus influenzae. In addition, several ureas with naphthyl substituents (4f, 4g, 4h) showed better activity in comparison to azithromycin against inducible resistant S. pyogenes. Ureas with naphthyl substituents 4g, 4h and thiourea 8h displayed moderate activity against constitutively resistant S. pneumoniae. (C) 2009 Elsevier Masson SAS. All rights reserved
• Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae
  作者：Mirjana Bukvić Krajačić、Miljenko Dumić、Predrag Novak、Mario Cindrić、Sanja Koštrun、Andrea Fajdetić、Sulejman Alihodžić、Karmen Brajša、Nedjeljko Kujundžić

  DOI：10.1016/j.bmcl.2010.11.079

  日期：2011.1

  A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N '' substituted 9a-(N'-carbamoyl-gamma-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-gamma-aminopropyl)- (7a,e), 9a-[N'-(beta-cyanoethyl)-N'-(carbamoyl-gamma-aminopropyl)]- (9a-c, 9g) 9a-[N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-gamma-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae. (C) 2010 Elsevier Ltd. All rights reserved.