(S)-2-((7-chloroquinolin-4-yl)amino)propanoic acid

• 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: (S)-2-((7-chloroquinolin-4-yl)amino)propanoic acid
• 英文别名: (2S)-2-[(7-chloroquinolin-4-yl)amino]propanoic acid
• 化学式: C₁₂H₁₁ClN₂O₂
• 分子量: 250.685
• InChiKey: XKWDVCNARHNXAL-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  (S)-2-((7-chloroquinolin-4-yl)amino)propanoic acid 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  基于组氨酸的强效抗疟药

  摘要：

  合成了一类新型组氨酸抗疟药的几种类似物。其中，化合物8g、8h和15表现出优异的抗疟活性。对接研究表明，这些抗疟药与其结合位点强烈相互作用。在表型测定中，发现化合物8 g抑制了寄生虫食物液泡中的血红蛋白降解。

  DOI：

  10.1002/cmdc.202200709
• 作为产物：
  描述：

  4,7-二氯喹啉 、 L-丙氨酸 以 苯酚 为溶剂， 生成 (S)-2-((7-chloroquinolin-4-yl)amino)propanoic 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

• 클로로퀸 기반 α,β-불포화아미드 유도체 화합물을 유효성분으로 함유하는 말라리아 감염 질환의 예방 또는 치료용 조성물
  申请人：Wonkwang University Center for Industry-Academy Cooperation 원광대학교산학협력단(220040233365) BRN ▼403-82-09152

  公开号：KR101653677B1

  公开（公告）日：2016-09-05

  본 발명은 신규 구조의 클로로퀸 기반 α,β-불포화아미드 유도체 화합물을 유효성분으로 함유하는 항말라리아제에 관한 것이다. 본 발명에 따른 신규 구조의 클로로퀸 기반 α,β-불포화아미드 유도체 화합물들을 대상으로 항-말라리아 활성을 P . falciparum 균주 성장 저해활성 및 Hela 세포 성장에 대한 세포독성실험을 통하여 확인한 결과, 상기 신규 화합물들의 항-말라리아 활성이 탁월함을 확인하여, 말라리아감염 질환 치료 및 예방용 약학조성물에 유용하게 이용될 수 있다.

  该专利涉及含有新结构的氯喹基α,β-不饱和酰胺衍生物化合物作为有效成分的抗疟药。通过对该新结构的氯喹基α,β-不饱和酰胺衍生物化合物进行抗疟活性P. falciparum菌株生长抑制活性和Hela细胞生长细胞毒性实验，确认了这些新化合物具有出色的抗疟活性，可用于治疗和预防疟疾感染疾病的药学组合物中。
• Design, synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine-resistant strain
  作者：Srinivasarao Kondaparla、Pooja Agarwal、Kumkum Srivastava、Sunil K. Puri、Seturam B. Katti

  DOI：10.1111/cbdd.12914

  日期：2017.6

  A series of novel bisquinoline compounds comprising N1 -(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the

  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。
• Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain
  作者：Manish Sinha、Vasanth R. Dola、Pooja Agarwal、Kumkum Srivastava、Wahajul Haq、Sunil K. Puri、Seturam B. Katti

  DOI：10.1016/j.bmc.2014.05.024

  日期：2014.7

  Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β(3)- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.
• Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery
  作者：Jianjun Cheng、Ryan Zeidan、Swaroop Mishra、Aijie Liu、Suzie H. Pun、Rajan P. Kulkarni、Gregory S. Jensen、Nathalie C. Bellocq、Mark E. Davis

  DOI：10.1021/jm060736s

  日期：2006.11.1

  To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N-4-(4-pyridinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N-4-(7-trifluoromethyl-4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N-4-(4-quinolinyl)-N-1, N-1-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.
• Histidinal‐Based Potent Antimalarial Agents
  作者：Chhuttan L. Meena、Tejashri Hingamire、Tanya Gupta、Bhagyashree Deshmukh、Krishanpal Karmodiya、Rakesh Joshi、Dhanasekaran Shanmugam、Gangadhar J. Sanjayan

  DOI：10.1002/cmdc.202200709

  日期：——

  Several analogs of a novel class of histidinal-based antimalarial agents were synthesised. Among them, compounds 8 g, 8 h, and 15 exhibited superior antimalarial activity. Docking studies revealed that these antimalarial agents strongly interact with their binding sites. In phenotypic assays, it was found that compound 8 g inhibited hemoglobin degradation in the parasite food vacuole.

  合成了一类新型组氨酸抗疟药的几种类似物。其中，化合物8g、8h和15表现出优异的抗疟活性。对接研究表明，这些抗疟药与其结合位点强烈相互作用。在表型测定中，发现化合物8 g抑制了寄生虫食物液泡中的血红蛋白降解。