9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-γ-aminopropyl]-9a-aza-9a-homoerithromycin A | 690255-34-6

• 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-[N'-(β-cyanoethyl)-γ-aminopropyl]-9a-aza-9a-homoerithromycin A
• 英文别名: 3-[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-trihydroxy-13-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,8,10,12,14-hexamethyl-15-oxo-1-oxa-6-azacyclopentadec-6-yl]propylamino]propanenitrile
• CAS: 690255-34-6
• 化学式: C₄₃H₈₀N₄O₁₂
• 分子量: 845.128
• InChiKey: TUONJOAVACLIIT-PFPZBMRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  59
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  216
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-γ-aminopropyl]-9a-aza-9a-homoerithromycin A 、 1-萘异硫氰酸酯 以 二氯甲烷 为溶剂， 反应 1.0h， 以36%的产率得到9-deoxo-9-dihydro-9a-(N'-(β-cyanoethyl)-N'-(1-naphthyl)thiocarbamoyl-γ-aminopropyl)-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Novel ureas and thioureas of 15-membered azalides with antibacterial activity against key respiratory pathogens

  摘要：

  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

  DOI：

  10.1016/j.ejmech.2009.02.001
• 作为产物：
  描述：

  9a-(3-aminopropyl)-9-deoxo-9a-aza-9a-homoerythromycin A 、 丙烯腈 以 甲醇 为溶剂， 反应 10.0h， 生成 9-deoxo-9-dihydro-9a-N-[N'-(β-cyanoethyl)-γ-aminopropyl]-9a-aza-9a-homoerithromycin A
  参考文献：
  名称：

  [EN] SUBSTITUTED 9a-N-[N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL]AND 9a-N-[N'-(B-CYANEOTHYL)-N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL]DERIVATIVES OF 9-DEOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCIN A AND 5-0-DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-AZA-HOMOERITHRONOLIDE A
  [FR] DERIVES DE 9-DESOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCINE A ET DE 5-0-DESOSAMINYL-9-DESOXO-9-DIHYDRO-9A-AZA-HOMOERITHRONOLIDE A SUBSTITUES PAR LE GROUPE 9A-N-[N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL] ET PAR LE GROUPE 9A-N-[N'-(B-CYANEOTHYL)-N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYLE]

  摘要：

  该发明涉及9-去氧-9-二氢-9a-氮杂-9a-同异赤霉素A和5-O-去甘霉素-9-去氧-9-二氢-9a-氮杂-9a-同异赤霉烯醇A的替代9a-N-[N'-(苯磺酰)羰基-Ϝ-氨基丙基]和9a-N-[N'-(β-氰乙基)-N'-(苯磺酰)羰基-Ϝ-氨基丙基]衍生物，这些是一种新型半合成的氮杂环大环内酯类抗生素，属于氮杂环大环内酯系列，其化学式为(I)，其中R代表H或克拉地诺基团，R1代表H或β-氰乙基基团，R2代表H或氟、氯和甲基基团，以及它们与无机或有机酸形成的药学上可接受的盐，以及用于制备药物组合物的方法，以及将它们的组合物用于消毒房间和医疗器械以及保护墙壁和木制涂层。

  公开号：

  WO2004043984A1

文献信息

• Novel Antimalarial 9A-Carbamoyl-Aminoalkyl and 9A-Thiocarbamoyl-Aminoalkyl Azalides
  申请人：Bukvic Krajacic Mirjana

  公开号：US20080200404A1

  公开（公告）日：2008-08-21

  Novel 9a-N′-substituted-carbamoyl- and thiocarbamoyl-aminoalkyl-9a-aza-9-deoxo-9-dihydro-9a-homoerythromycin A and 3-O-decladinosyl-9a-aza-9-deoxo-9-dihydro-9a-homoerythromycin A compounds having antimalarial activity are claimed. More particularly, the invention relates to 9a-N′-substituted-carbamoyl- and thiocarbamoyl-β-aminoethyl- or -γ-aminopropyl-9a-aza-9-deoxo-9-dihydro-9a-homoerythromycin A and 3-O-decladinosyl-9a-aza-9-deoxo-9-dihydro-9a-homoerythromycin A compounds and to pharmaceutically acceptable derivatives thereof having antimalarial activity.

  本发明涉及具有抗疟活性的9a-N'-取代-氨基甲酰基和硫代氨基甲酰基-氨基烷基-9a-氮杂-9-去氧-9-二氢-9a-同源红霉素A和3-O-去氯基-9a-氮杂-9-去氧-9-二氢-9a-同源红霉素A化合物。更具体地，该发明涉及具有抗疟活性的9a-N'-取代-氨基甲酰基和硫代氨基甲酰基-β-氨基乙基或-γ-氨基丙基-9a-氮杂-9-去氧-9-二氢-9a-同源红霉素A和3-O-去氯基-9a-氮杂-9-去氧-9-二氢-9a-同源红霉素A化合物及其具有抗疟活性的药用可接受衍生物。
• [EN] SUBSTITUTED 9a-N-[N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL]AND 9a-N-[N'-(B-CYANEOTHYL)-N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL]DERIVATIVES OF 9-DEOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCIN A AND 5-0-DESOSAMINYL-9-DEOXO-9-DIHYDRO-9A-AZA-HOMOERITHRONOLIDE A<br/>[FR] DERIVES DE 9-DESOXO-9-DIHYDRO-9A-AZA-9A-HOMOERITHROMYCINE A ET DE 5-0-DESOSAMINYL-9-DESOXO-9-DIHYDRO-9A-AZA-HOMOERITHRONOLIDE A SUBSTITUES PAR LE GROUPE 9A-N-[N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYL] ET PAR LE GROUPE 9A-N-[N'-(B-CYANEOTHYL)-N'-(BENZENESULFONYL)CARBAMOYL-Y-AMINOPROPYLE]
  申请人：PLIVA D D

  公开号：WO2004043984A1

  公开（公告）日：2004-05-27

  The invention relates to substituted 9a-N-[N’-(benzenesulfonyl)carbamoyl-Ϝ-aminopropyl] and 9a-N-[N’-(β-cyanoethyl)-N’-(benzenesulfonyl)carbamoyl-Ϝ-aminopropyl] derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerithromycin A and 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerithronolide A, novel semisynthetic macrolide antibiotics of the azalide series, of the formula (I) wherein R represents H or cladinosyl moiety, R1 represents H or β-cyanoethyl group an R2 represents H or fluoro, chloro and methyl group, and pharmaceutically acceptable salts thereof with inorganic or organic acids, to the process for the preparation of pharmaceutical compositions as well as to the use their compositions for sterilization rooms and medical instruments as well as for protection of wall and wooden coatings.

  该发明涉及9-去氧-9-二氢-9a-氮杂-9a-同异赤霉素A和5-O-去甘霉素-9-去氧-9-二氢-9a-氮杂-9a-同异赤霉烯醇A的替代9a-N-[N'-(苯磺酰)羰基-Ϝ-氨基丙基]和9a-N-[N'-(β-氰乙基)-N'-(苯磺酰)羰基-Ϝ-氨基丙基]衍生物，这些是一种新型半合成的氮杂环大环内酯类抗生素，属于氮杂环大环内酯系列，其化学式为(I)，其中R代表H或克拉地诺基团，R1代表H或β-氰乙基基团，R2代表H或氟、氯和甲基基团，以及它们与无机或有机酸形成的药学上可接受的盐，以及用于制备药物组合物的方法，以及将它们的组合物用于消毒房间和医疗器械以及保护墙壁和木制涂层。
• 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