4-[(7-chloro-4-quinolinyl)amino]butanoic acid | 874918-61-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[(7-chloro-4-quinolinyl)amino]butanoic acid
• 英文别名: 4-[(7-Chloroquinolin-1-ium-4-yl)amino]butanoate
• CAS: 874918-61-3
• 化学式: C₁₃H₁₃ClN₂O₂
• mdl: MFCD09948578
• 分子量: 264.711
• InChiKey: AMBJNYSPRIYZPR-UHFFFAOYSA-N

物化性质

• 沸点：
  512.1±45.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(7-chloro-4-quinolinyl)amino]butanoic acid 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、320.01 kPa 条件下， 反应 5.5h， 生成 2'-O-[3-({4-[(4-quinolinyl)amino]butanoyl}amino)propyl]-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Design, Synthesis, and in Vitro Activity of Novel 2′-O-Substituted 15-Membered Azalides

  摘要：

  Malaria remains one of the most widespread human infectious diseases, and its eradication will largely depend on antimalarial drug discovery. Here, we present a novel approach to the development of the azalide class of antimalarials by describing the design, synthesis, and characterization of novel 2'-O-substituted-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives consisting of different quinoline moieties covalently liked to a 15-membered azalide scaffold at position 2'. By multistep straightforward synthesis, 19 new, stable, and soluble compounds were created and biologically profiled. Most active compounds from the 4-amino-7-chloroquinoline series showed high selectivity for P. falciparum parasites, and in vitro antimalarial activity improved 1000-fold over azithromycin. Antimalarial potency was equivalent to chloroquine against the sensitive strain (3D7A) and up to 48-fold enhanced over chloroquine against the chloroquine-resistant strain (W2). Concurrently, the antibacterial activity of the compounds was eliminated, thus facilitating the development of malaria-specific macrolide agents.

  DOI：

  10.1021/jm201676t
• 作为产物：
  描述：

  4,7-二氯喹啉 、 4-氨基丁酸 以 苯酚 为溶剂， 反应 18.0h， 生成 4-[(7-chloro-4-quinolinyl)amino]butanoic acid
  参考文献：
  名称：

  4-Aminoquinoline-β-Lactam Conjugates: Synthesis, Antimalarial, and Antitubercular Evaluation

  摘要：

  A library of quinoline‐β‐lactam‐based hybrids was synthesized and tested for their antimalarial and antitubercular activities. The present antimalarial data showed the dependence of activity on the nature of linker, N‐1 substituent of the β‐lactam ring as well as the length of alkyl chain. Most of the compounds are not as efficient as chloroquine in inhibiting the culture growth of Plasmodium falciparum W2 strain. Nevertheless, the synthesized hybrids showed better antitubercular activities (up to five times) compared with cephalexin (up to three times) and ethionamide.

  DOI：

  10.1111/cbdd.12225

文献信息

• [EN] 3'-N-SUBSTITUTED 9-DEOXO-9A-METHYL-9A-AZA-HOMOERYTHROMYCIN HAVING ANTIMALARIAL ACTIVITY<br/>[FR] 9-DÉOXO-9A-MÉTHYL-9A-AZAHOMOÉRYTHROMYCINE 3'-N-SUBSTITUÉE AYANT UNE ACTIVITÉ ANTIPALUDIQUE
  申请人：GLAXOSMITHKLINE ZAGREB

  公开号：WO2010086351A1

  公开（公告）日：2010-08-05

  The present invention relates to novel 3'-N-substituted 9-deoxo-9a-methyl-9a-aza-9a- homoerythromycin A derivatives having antimalarial activity. More particularly, the invention relates to 3'-N-substituted-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A and 3'-N-substituted-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives having antimalarial activity, to the intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof having antimalarial activity.

  本发明涉及具有抗疟疾活性的新型3'-N-取代9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A衍生物。更具体地，本发明涉及具有抗疟疾活性的3'-N-取代9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A和3'-N-取代3-O-去氯鼠杆菌素-9-去氧-9a-甲基-9a-氮杂-9a-同麦红霉素A衍生物，以及它们的制备中间体、制备方法、用作治疗剂的用途以及具有抗疟疾活性的盐。
• Compounds
  申请人：Alihodzic Sulejman

  公开号：US20090036388A1

  公开（公告）日：2009-02-05

  The present invention relates to novel 2′-O-substituted 9-deoxo-9 a -methyl-9 a -aza-9 a -homoerythromycin A derivatives having antimalarial activity. More particularly, the invention relates to 2′-O-substituted-9-deoxo-9 a -methyl-9 a -aza-9 a -homoerythromycin A and 2′-O-substituted-3-O-decladinosyl-9-deoxo-9 a -methyl-9 a -aza-9 a -homoerythromycin A derivatives having antimalarial activity, to the intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof having antimalarial activity.

  本发明涉及具有抗疟活性的新型2'-O-取代的9-去氧-9a-甲基-9a-氮-9a-同异红霉素A衍生物。更具体地，本发明涉及具有抗疟活性的2'-O-取代-9-去氧-9a-甲基-9a-氮-9a-同异红霉素A和2'-O-取代-3-O-去氧-9-去氧-9a-甲基-9a-氮-9a-同异红霉素A衍生物，以及它们的制备中间体、制备方法、用作治疗剂的用途以及具有抗疟活性的盐。
• Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents
  作者：Kristina Starčević、Dijana Pešić、Ana Toplak、Goran Landek、Sulejman Alihodžić、Esperanza Herreros、Santiago Ferrer、Radan Spaventi、Mihaela Perić

  DOI：10.1016/j.ejmech.2012.01.039

  日期：2012.3

  Malaria remains the most prevalent tropical disease, and due to the spread of resistant parasites novel therapeutics are urgently needed. Azithromycin has shown potential in malaria treatment so we designed hybrid azalide molecules with the aim to improve activity against and selectivity for the malaria parasite. Novel hybrid molecules comprising 4-aminoquinoline moiety covalently liked to 15-membered azalide scaffold at position C-3' were synthesized and biologically evaluated. Antimalarial testing against Plasmodium falciparum sensitive and resistant strains confirmed the improved in vitro activity over azithromycin and chloroquine. Selectivity of the compounds (HepG2 IC50/P. falciparum IC50 ratio) for the parasite was high (100-2700) and their antibacterial activity diminished. Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.
• 9-DEOXO-9A-METHYL-9A-AZA-9A-HOMOERYTHROMYCIN A DERIVATIVES AND THEIR USE FOR THE TREATMENT OF MALARIA
  申请人：GlaxoSmithKline istrazivacki centar Zagreb d.o.o.

  公开号：EP2183265A1

  公开（公告）日：2010-05-12
• [EN] 9-DEOXO-9A-METHYL-9A-AZA-9A-HOMOERYTHROMYCIN A DERIVATIVES AND THEIR USE FOR THE TREATMENT OF MALARIA<br/>[FR] DÉRIVÉS DE 9-DÉSOXO-9A-MÉTHYL-9A-AZA-9A-HOMOÉRYTHROMYCINE A ET LEURS UTILISATIONS POUR LE TRAITEMENT DE LA MALARIA
  申请人：GLAXOSMITHKLINE ZAGREB

  公开号：WO2009016142A1

  公开（公告）日：2009-02-05

  The present invention relates to novel 2'-O-substituted 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives having antimalarial activity. More particularly, the invention relates to 2'-O-substituted-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A and 2'-O-substituted-3-O-decladinosyl-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A derivatives having antimalarial activity, to the intermediates for their preparation, to the methods for their preparation, to their use as therapeutic agents, and to salts thereof having antimalarial activity.