4-((3-bromopropyl)thio)-7-chloroquinoline | 1033132-67-0

• 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: 4-((3-bromopropyl)thio)-7-chloroquinoline
• CAS: 1033132-67-0
• 化学式: C₁₂H₁₁BrClNS
• 分子量: 316.649
• InChiKey: ALVLUWRDLXQZNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.77
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  12.89
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-((3-bromopropyl)thio)-7-chloroquinoline 、 二乙胺 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以0.8 g的产率得到S-(7-chloro-4-quinolyl)-3-(N,N-diethylamino)propanethiol
  参考文献：
  名称：

  4-N-, 4-S-, and 4-O-Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pK_a on Activity vs Chloroquine Resistant Malaria

  摘要：

  Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pK(a) of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs mu-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.

  DOI：

  10.1021/jm701478a
• 作为产物：
  描述：

  7-Chloro-1H-quinoline-4-thione 、 1,3-二溴丙烷 在 氢氧化钾 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 4-((3-bromopropyl)thio)-7-chloroquinoline
  参考文献：
  名称：

  4-N-, 4-S-, and 4-O-Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pK_a on Activity vs Chloroquine Resistant Malaria

  摘要：

  Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pK(a) of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs mu-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.

  DOI：

  10.1021/jm701478a