9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithronolide A | 690258-31-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithronolide A
• 英文别名: 4-[[(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-azacyclopentadecane-6-carbonyl]amino]benzenesulfonyl chloride
• CAS: 690258-31-2
• 化学式: C₃₆H₆₀ClN₃O₁₂S
• 分子量: 794.404
• InChiKey: QQPGMFFKJOHBDA-AFCUZKIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  53
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  224
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithronolide A 在 ammonium hydroxide 作用下， 反应 2.0h， 生成 5-O-desosaminyl-9-deoxo-9-dihydro-9a-N-[4-(aminosulfonylphenyl)-carbamoyl]-9a-aza-9a-homoerithronolide A
  参考文献：
  名称：

  Azithromycin–sulfonamide conjugates as inhibitors of resistant Streptococcus pyogenes strains

  摘要：

  Novel hybrid compounds 6a-6d, conjugates of 15-membered azalides and sulfonamides, i.e. unsubstituted, 4-aryl- and 4-heteroaryl-amino-sulfonyl derivatives of 9a-[N'-(phenylcarbamoyl)]-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A were synthesized and characterized by IR, one- and two-dimensional NMR spectroscopies and MALDI-TOF and MS/MS mass spectrometry.The new compounds were evaluated in vitro against a panel of sensitive and resistant Gram-positive and Gram-negative bacterial strains. 9a-{N'-[4-(Aminosulfonyl)phenyl]carbamoyl) - (6a) and 9a-{N'-[4-(phenylaminosulfonyl)phenyl]carbamoyl) - (6b) derivatives showed improvements in activity against inducible resistant Streptococcus pyogenes in comparison with macrolide antibiotic azithromycin and starting material 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2). In addition, the synthesized azithromycin-sulfonamide conjugates 6a-6d showed good antibacterial activity against sensitive S. pyogenes and Streptococcus pneumoniae strains.The kinetics of degradation in the artificial gastric juice showed that the most active compounds, 6a and 6b, exhibited azithromycin like stability. The cleavage of the cladinose sugar was found to be the main decomposition pathway leading to inactive 7a and 7b, prepared also as analytical standards by the alternative synthetic route together with 7c and 7d. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.08.008
• 作为产物：
  描述：

  阿奇霉素 A 在 盐酸 作用下， 以 甲苯 为溶剂， 反应 14.0h， 生成 9-deoxo-9-dihydro-9a-N-{[4-(chlorosulfonyl)phenyl]-carbamoyl}-9a-aza-9a-homoerithronolide A
  参考文献：
  名称：

  Azithromycin–sulfonamide conjugates as inhibitors of resistant Streptococcus pyogenes strains

  摘要：

  Novel hybrid compounds 6a-6d, conjugates of 15-membered azalides and sulfonamides, i.e. unsubstituted, 4-aryl- and 4-heteroaryl-amino-sulfonyl derivatives of 9a-[N'-(phenylcarbamoyl)]-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A were synthesized and characterized by IR, one- and two-dimensional NMR spectroscopies and MALDI-TOF and MS/MS mass spectrometry.The new compounds were evaluated in vitro against a panel of sensitive and resistant Gram-positive and Gram-negative bacterial strains. 9a-{N'-[4-(Aminosulfonyl)phenyl]carbamoyl) - (6a) and 9a-{N'-[4-(phenylaminosulfonyl)phenyl]carbamoyl) - (6b) derivatives showed improvements in activity against inducible resistant Streptococcus pyogenes in comparison with macrolide antibiotic azithromycin and starting material 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2). In addition, the synthesized azithromycin-sulfonamide conjugates 6a-6d showed good antibacterial activity against sensitive S. pyogenes and Streptococcus pneumoniae strains.The kinetics of degradation in the artificial gastric juice showed that the most active compounds, 6a and 6b, exhibited azithromycin like stability. The cleavage of the cladinose sugar was found to be the main decomposition pathway leading to inactive 7a and 7b, prepared also as analytical standards by the alternative synthetic route together with 7c and 7d. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.08.008

文献信息

• [EN] SUBSTITUTED 9A-N-{N'-[4-(SULFONYL)PHENYL]CARBAMOYL} DERIVATIVES OF 9-DEOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCIN A AND 5-0-DESOSAMINYL­-9-DEOXO-9-DI-HYDRO-9A-AZA-9A-HOMOERITHRONOLIDE A<br/>[FR] DERIVES DE 9-DESOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCINE A ET DE 5-0-DESOSAMINYL--9-DESOXO-9-DI-HYDRO-9A-AZA-9A-HOMOERITHRONOLIDE A SUBSTITUES PAR LE GROUPE 9A-N-{N'-[4-(SULFONYL)PHENYL]CARBAMOYL}
  申请人：PLIVA D D

  公开号：WO2004043985A1

  公开（公告）日：2004-05-27

  The invention relates to substituted 9a-N-N'-[4-(sulfonyl)phenyl]carbamoyl} derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerithromycin A and 5-0-desosaminyl­-9-deoxo-9-di-hydro-9a-aza-9a-homoerithronolide A, novel semisynthetic macrolide antibiotics of the azalide series general formula (1), wherein R represents H or cladinosyl moiety and R1 represents chloro, amino, phenylamino, 2-pyridylamino, 3,4-dimethyl-4-isoxazolylamino and 5-methyl-3­-isoxazolylamino group, and pharmaceutically acceptable addition salts thereof with inorganic or organic acids, to the process for their preparation of pharmaceutical composition as well as the use their compositions for sterilization rooms and medical instruments as well as for protection of wall and wooden coatings.

  本发明涉及9-去氧-9-二氢-9a-氮杂-9a-同麻黄胺霉素A和5-O-去甲基鲍鱼糖基-9-去氧-9-二氢-9a-氮杂-9a-同麻黄内酯A的取代9a-N-N'-[4-(磺酰基)苯基]氨基甲酰}衍生物，是一种新型半合成大环内酯类抗生素，其一般式为(1)，其中R代表H或克拉地诺西尔基团，R1代表氯、氨基、苯基氨基、2-吡啶基氨基、3,4-二甲基-4-异噁唑基氨基和5-甲基-3-异噁唑基氨基基团，以及它们与无机或有机酸的药学上可接受的加成盐，以及它们的制备过程、制药组合物的使用以及用于消毒房间和医疗器械以及保护墙壁和木质涂层的组合物的使用。
• Azithromycin–sulfonamide conjugates as inhibitors of resistant Streptococcus pyogenes strains
  作者：Mirjana Bukvić Krajačić、Predrag Novak、Mario Cindrić、Karmen Brajša、Miljenko Dumić、Nedjeljko Kujundžić

  DOI：10.1016/j.ejmech.2006.08.008

  日期：2007.2

  Novel hybrid compounds 6a-6d, conjugates of 15-membered azalides and sulfonamides, i.e. unsubstituted, 4-aryl- and 4-heteroaryl-amino-sulfonyl derivatives of 9a-[N'-(phenylcarbamoyl)]-9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A were synthesized and characterized by IR, one- and two-dimensional NMR spectroscopies and MALDI-TOF and MS/MS mass spectrometry.The new compounds were evaluated in vitro against a panel of sensitive and resistant Gram-positive and Gram-negative bacterial strains. 9a-N'-[4-(Aminosulfonyl)phenyl]carbamoyl) - (6a) and 9a-N'-[4-(phenylaminosulfonyl)phenyl]carbamoyl) - (6b) derivatives showed improvements in activity against inducible resistant Streptococcus pyogenes in comparison with macrolide antibiotic azithromycin and starting material 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2). In addition, the synthesized azithromycin-sulfonamide conjugates 6a-6d showed good antibacterial activity against sensitive S. pyogenes and Streptococcus pneumoniae strains.The kinetics of degradation in the artificial gastric juice showed that the most active compounds, 6a and 6b, exhibited azithromycin like stability. The cleavage of the cladinose sugar was found to be the main decomposition pathway leading to inactive 7a and 7b, prepared also as analytical standards by the alternative synthetic route together with 7c and 7d. (c) 2006 Elsevier Masson SAS. All rights reserved.