2-(7-chloroquinolin-4-ylamino)acetic acid | 854705-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(7-chloroquinolin-4-ylamino)acetic acid
• 英文别名: 2-[(7-Chloroquinolin-1-ium-4-yl)amino]acetate
• CAS: 854705-48-9
• 化学式: C₁₁H₉ClN₂O₂
• mdl: MFCD09943129
• 分子量: 236.658
• InChiKey: DZWITQVBNUNXOK-UHFFFAOYSA-N

物化性质

• 熔点：
  253-255 °C (decomp)
• 沸点：
  494.7±40.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 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：

  2-(7-chloroquinolin-4-ylamino)acetic acid 在 盐酸 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.68h， 生成 2'-O-[3-({2-[(7-chloro-4-quinolinyl)amino]ethanoyl}amino)propyl]-3-O-decladinosyl-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 、 聚甘氨酸 以 苯酚 为溶剂， 生成 2-(7-chloroquinolin-4-ylamino)acetic acid
  参考文献：
  名称：

  一些双喹啉类药物对氯喹抗性菌株的设计，合成及体外抗疟原虫活性。

  摘要：

  一系列新的双喹啉化合物，包括N1-（7-氯喹啉-4-基）乙烷-1，2-二胺和7-氯-N-（2-（哌嗪-1-基）乙基）喹啉-4-胺描述了含有含有各种氨基酸的7-氯-4-氨基喹啉的衍生物。我们已经在体外对化合物对恶性疟原虫的氯喹敏感（3D7）和氯喹抗性（K1）菌株进行了生物评估。在该系列中，化合物4和7与氯喹（CQ; IC50 = 0.255 +/- 0.049 mum）相比，对K1菌株表现出1.8倍和10.6倍的优异活性，IC50值分别为0.137 +/- 0.014和0.026 +/-。分别为0.007妈妈。此外，与CQ相比，化合物7还显示出对恶性疟原虫的3D7菌株（IC50 = 0.024 +/- 0.003微米）有希望的活性。该系列中的所有化合物均显示出0.57至4之间的电阻系数。CQ为71，而CQ为51。这些结果表明，作为对氯喹抗性恶性疟原虫有活性的新型抗疟药，可以研究双喹啉类化合物的进一步开发。

  DOI：

  10.1111/cbdd.12914

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。
• Hybrid molecules QA, wherein Q is an aminoquinoline and a is an antibiotic or a resistance enzyme inhibitor, their synthesis and their uses as antibacterial agent
  申请人：Sanchez Muriel

  公开号：US20060025327A1

  公开（公告）日：2006-02-02

  Aminoquinoline-antibiotic hybrid compounds in the form of hybrid molecules QA, wherein Q is an aminoquinoline and A is an antibiotic or a resistance enzyme inhibitor, their synthesis and their uses as antibacterial agent. This compound is defined by the general formula (I): Q-(Y 1 ) p —(U) p′ —(Y 2 ) p″ -A  (I) in which Q represents an aminoquinoline, (Y 1 ) p —(U) p′ —(Y 2 ) p″ — is an optional spacer arm and A is an antibiotic, one of its derivatives or precursors, or a resistance enzyme inhibitor. The invention unexpectedly enables the activity of the antibiotic to be improved.

  氨基喹啉-抗生素混合物化合物以混合分子QA的形式存在，其中Q是氨基喹啉，A是抗生素或耐药酶抑制剂，它们的合成及用途作为抗菌剂。该化合物由通用公式(I)定义：Q-(Y1)p—(U)p′—(Y2)p″-A  (I)其中Q代表氨基喹啉，(Y1)p—(U)p′—(Y2)p″—为可选的间隔臂，A是抗生素、其衍生物或前体之一，或耐药酶抑制剂。该发明意外地能够改善抗生素的活性。
• 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。
• Hybrid molecules QA where Q is an aminoquinoline and A is an antibiotic residue, the synthesis and uses thereof as antibacterial agents
  申请人：Sanchez Muriel

  公开号：US20070060558A1

  公开（公告）日：2007-03-15

  The invention concerns an aminoquinoline-antibiotic hybrid compound of general formula (I): Q—(Y 1 ) p —(U) p —(Y 2 ) p -A: wherein Q represents an aminoquinoline, (Y 1 ) p (U) p —(Y 2 ) p″ is an optional spacer and A is an antibiotic residue. The invention enables the antibiotic residue activity to be unexpectedly enhanced.

  本发明涉及一种氨基喹啉-抗生素杂合物，其一般式为(I)：Q—(Y1)p—(U)p—(Y2)p-A，其中Q代表氨基喹啉，(Y1)p(U)p—(Y2)p″是可选的间隔基，A为抗生素残基。本发明使得抗生素残基的活性得到了意外的增强。
• Design and synthesis of harmiquins, harmine and chloroquine hybrids as potent antiplasmodial agents
  作者：Goran Poje、Lais Pessanha de Carvalho、Jana Held、Diana Moita、Miguel Prudêncio、Ivana Perković、Tana Tandarić、Robert Vianello、Zrinka Rajić

  DOI：10.1016/j.ejmech.2022.114408

  日期：2022.8

  significantly higher activity than CQ against the resistant Plasmodium strains and had a very high selectivity index (4450). Harmiquins may act through the inhibition of heme polymerization and binding to the ATP binding site of the PfHsp90, which would explain their increased activity against the CQ-resistant Plasmodium strains. These results establish harmiquins as valuable antiplasmodial hits for future

  疟疾仍然是世界范围内的主要健康问题之一。缺乏有效的疫苗以及疟原虫对已批准的抗疟药物的耐药性增加，需要开发能够有效预防和/或治疗这种疾病的新型抗疟原虫药物。 Harmiquins 代表在一个分子中结合具有不同抗疟原虫活性机制的两个部分的杂种，即已知抑制血红素聚合的氯喹 (CQ) 支架和能够与恶性疟原虫热休克蛋白 90 ( Pf ) 结合的 β-咔啉环。热休克蛋白90)。在这里，我们介绍了它们的合成、生物活性的评价和潜在的作用机制。合成的杂化物在所使用的接头类型（三唑环或酰胺键）以及在harmine的β-咔啉核心上的取代位置不同。针对疟原虫的红细胞阶段评估了harmiquins的抗疟原虫活性生命周期，并在 HepG2 细胞上测试了它们的细胞毒作用。结果表明，harmiquins 对 CQ 敏感（Pf 3D7）和 CQ 抗性（Pf Dd2、Pf K1 和Pf 7G8）均具有显着的活性。恶性疟原虫