6-chloro-3-iodo-2-methylquinolin-4(1H)-one | 1228284-42-1

• 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: 6-chloro-3-iodo-2-methylquinolin-4(1H)-one
• 英文别名: 6-chloro-3-iodo-2-methyl-1H-quinolin-4-one
• CAS: 1228284-42-1；65673-92-9
• 化学式: C₁₀H₇ClINO
• 分子量: 319.529
• InChiKey: JUXWCUNUJNDZMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-3-iodo-2-methylquinolin-4(1H)-one 在 2-双环己基膦-2',6'-二甲氧基联苯 、 1,1'-双(二苯基膦)二茂铁 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 锌 作用下， 以 2,4-滴二甲胺盐 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 3-(furan-2-yl)-1,2-dimethyl-4-oxo-1,4-dihydroquinoline-6-carbonitrile
  参考文献：
  名称：

  Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings

  摘要：

  A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.

  DOI：

  10.1021/jo1014504
• 作为产物：
  描述：

  3-((4-氯苯基)亚氨基)丁酸乙酯 在 dowtherm A 、 碘 、 正丁胺 、 potassium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 6-chloro-3-iodo-2-methylquinolin-4(1H)-one
  参考文献：
  名称：

  Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers

  摘要：

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.

  DOI：

  10.1021/jm500147k

文献信息

• 10.3390/molecules29153615
  作者：Senkina, Julia、Knapp, Spencer

  DOI：10.3390/molecules29153615

  日期：——

  qualities, the antimalarial endochin-like quinolone (ELQ) scaffold has been modified by replacing the 4-(trifluoromethoxy)phenyl portion with an isoidide unit that is further adjustable by varying the distal O-substituents. As expected, the water solubilities of the new analogs are greatly improved, and the melting points are lower. However, the antimalarial potency of the new analogs is reduced to

  为了提高药物相似性，抗疟内啡肽样喹诺酮 (ELQ) 支架已通过用异艾杜单元替换 4-(三氟甲氧基)苯基部分进行了修改，异艾杜单元可通过改变远端 O 取代基进一步调节。正如预期的那样，新类似物的水溶性大大提高，并且熔点更低。然而，新类似物的抗疟效力降低至 EC50 > 1 毫摩尔，这是由于新替代物的亲水性所致。
• Discovery, Synthesis, and Optimization of Antimalarial 4(1<i>H</i>)-Quinolone-3-Diarylethers
  作者：Aaron Nilsen、Galen P. Miley、Isaac P. Forquer、Michael W. Mather、Kasiram Katneni、Yuexin Li、Sovitj Pou、April M. Pershing、Allison M. Stickles、Eileen Ryan、Jane Xu Kelly、J. Stone Doggett、Karen L. White、David J. Hinrichs、Rolf W. Winter、Susan A. Charman、Lev N. Zakharov、Ian Bathurst、Jeremy N. Burrows、Akhil B. Vaidya、Michael K. Riscoe

  DOI：10.1021/jm500147k

  日期：2014.5.8

  The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers. The initial prototype, ELQ-233, exhibited low nanomolar IC50 values against all tested strains including clinical isolates harboring resistance to atovaquone. ELQ-271 represented the next critical step in the iterative optimization process, as it was stable to metabolism and highly effective in vivo. Continued analoging revealed that the substitution pattern on the benzenoid ring of the quinolone core significantly influenced reactivity with the host enzyme. This finding led to the rational design of highly selective ELQs with outstanding oral efficacy against murine malaria that is superior to established antimalarials chloroquine and atovaquone.
• Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings
  作者：R. Matthew Cross、Roman Manetsch

  DOI：10.1021/jo1014504

  日期：2010.12.17

  A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.