(4-Chloro-phenyl)-((2R,4S)-2,6-dimethyl-4-p-tolylamino-3,4-dihydro-2H-quinolin-1-yl)-methanone

• 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-Chloro-phenyl)-((2R,4S)-2,6-dimethyl-4-p-tolylamino-3,4-dihydro-2H-quinolin-1-yl)-methanone
• 英文别名: (4-chlorophenyl)-[(2R,4S)-2,6-dimethyl-4-(4-methylanilino)-3,4-dihydro-2H-quinolin-1-yl]methanone
• 化学式: C₂₅H₂₅ClN₂O
• 分子量: 404.939
• InChiKey: IOWNGZFGTXBYQO-JPYJTQIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  乙烷,三氯氟- 在 吡啶 、 T406石油添加剂 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 96.0h， 生成 (4-Chloro-phenyl)-((2R,4S)-2,6-dimethyl-4-p-tolylamino-3,4-dihydro-2H-quinolin-1-yl)-methanone
  参考文献：
  名称：

  Structural requirement and stereospecificity of tetrahydroquinolines as potent ecdysone agonists

  摘要：

  Tetrahydroquinoline (THQ)- type compounds are a class of potential larvicides against mosquitoes. The structure-activity relationships (SAR) of these compounds were previously investigated (Smith et al., Bioorg. Med. Chem. Lett. 2003, 13, 1943-1946), and one of cis-forms (with respect to the configurations of 2-methyl and 4-anilino substitutions on the THQ basic structure) was stereoselectively synthesized. However, the absolute configurations of C2 and C4 were not determined. In this study, four THQ-type compounds with cis configurations were synthesized, and two were submitted for X-ray crystal structure analysis. This analysis demonstrated that two enantiomers are packed into the crystal form. We synthesized the cis-form of the fluorinated THQ compound, according to the published method, and the enantiomers were separated via chiral HPLC. The absolute configurations of the enantiomers were determined by X-ray crystallography. Each of the enantiomers was tested for activity against mosquito larvae in vivo and competitive binding to the ecdysone receptor in vitro. Compared to the (2S, 4R) enantiomer, the (2R, 4S) enantiomer showed 55 times higher activity in the mosquito larvicidal assay, and 36 times higher activity in the competitive receptor binding assay. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.043

文献信息

• Synthesis and SAR of cis-1-Benzoyl-1,2,3,4-tetrahydroquinoline ligands for control of gene expression in ecdysone responsive systems
  作者：Howard C Smith、Caitlin K Cavanaugh、Jennifer L Friz、Christine S Thompson、Jessica A Saggers、Enrique L Michelotti、Javier Garcia、Colin M Tice

  DOI：10.1016/s0960-894x(03)00317-2

  日期：2003.6

  A library of 35 cis-1-benzoyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolines was prepared. The compounds bore various substitutuents on the benzoyl ring, at the 4-position of the phenylamino ring and at the 6-position of the tetrahydroquinoline ring. The compounds were assayed for their ability to cause expression of a reporter gene downstream of an ecdysone response element in a mammalian cell line engineered to express the ecdysone receptor from Aedes aegypti. In general, compounds with small lipophilic substituents at the meta and para-positions of the benzoyl ring and hydrogen or fluorine at the 4-position of the phenylamino ring and the 6-position of the tetrahydroquino line ring were the most potent. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Structural requirement and stereospecificity of tetrahydroquinolines as potent ecdysone agonists
  作者：Seiya Kitamura、Toshiyuki Harada、Hajime Hiramatsu、Ryo Shimizu、Hisashi Miyagawa、Yoshiaki Nakagawa

  DOI：10.1016/j.bmcl.2014.02.043

  日期：2014.4

  Tetrahydroquinoline (THQ)- type compounds are a class of potential larvicides against mosquitoes. The structure-activity relationships (SAR) of these compounds were previously investigated (Smith et al., Bioorg. Med. Chem. Lett. 2003, 13, 1943-1946), and one of cis-forms (with respect to the configurations of 2-methyl and 4-anilino substitutions on the THQ basic structure) was stereoselectively synthesized. However, the absolute configurations of C2 and C4 were not determined. In this study, four THQ-type compounds with cis configurations were synthesized, and two were submitted for X-ray crystal structure analysis. This analysis demonstrated that two enantiomers are packed into the crystal form. We synthesized the cis-form of the fluorinated THQ compound, according to the published method, and the enantiomers were separated via chiral HPLC. The absolute configurations of the enantiomers were determined by X-ray crystallography. Each of the enantiomers was tested for activity against mosquito larvae in vivo and competitive binding to the ecdysone receptor in vitro. Compared to the (2S, 4R) enantiomer, the (2R, 4S) enantiomer showed 55 times higher activity in the mosquito larvicidal assay, and 36 times higher activity in the competitive receptor binding assay. (c) 2014 Elsevier Ltd. All rights reserved.