(E)-3-(6-chloro-4-(4-fluorophenyl) quinolin-2-yl)-1-(3-((dimethylamino) methyl)-4-hydroxyphenyl) prop-2-en-1-one | 1594133-63-7

• 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: (E)-3-(6-chloro-4-(4-fluorophenyl) quinolin-2-yl)-1-(3-((dimethylamino) methyl)-4-hydroxyphenyl) prop-2-en-1-one
• 英文别名: (E)-3-[6-chloro-4-(4-fluorophenyl)quinolin-2-yl]-1-[3-[(dimethylamino)methyl]-4-hydroxyphenyl]prop-2-en-1-one
• CAS: 1594133-63-7
• 化学式: C₂₇H₂₂ClFN₂O₂
• 分子量: 460.935
• InChiKey: QIXBXQZHPDVZNY-FMIVXFBMSA-N

物化性质

• 沸点：
  636.8±55.0 °C(predicted)
• 密度：
  1.303±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氯-2-甲基-4-羟基喹啉 在 selenium(IV) oxide 、 四(三苯基膦)钯 、 硫酸 、 三溴化磷 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (E)-3-(6-chloro-4-(4-fluorophenyl) quinolin-2-yl)-1-(3-((dimethylamino) methyl)-4-hydroxyphenyl) prop-2-en-1-one
  参考文献：
  名称：

  Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs

  摘要：

  In vitro ADME characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA model (31 x 10(-6) cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. Compound 1 was found to have no CYP450 liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with an IC50 value of 0.50 mu M. Analogs of 1 were synthesized and subsequently characterized for in vitro activity against the intracellular form of Leishmania donovani. Resulting quinolines were found to have similar efficacy as 1 against the parasite. Compounds 8b and 8f were found to be the most active with IC50 values of 0.84 mu M and 0.17 mu M, respectively compared to 0.22 mu M for compound 1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver microsomes but lost the efficacy with an IC50 of 6.42 mu M. Based on the in vitro efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be screened in further assays. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.065

文献信息

• Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs
  作者：Vadiraj S. Gopinath、Mukkavilli Rao、Rahul Shivahare、Preeti Vishwakarma、Sweta Ghose、Ashok Pradhan、Ramamohan Hindupur、Koushik Das Sarma、Suman Gupta、Sunil K. Puri、Delphine Launay、Denis Martin

  DOI：10.1016/j.bmcl.2014.03.065

  日期：2014.5

  In vitro ADME characterization of the lead compound 1 identified for visceral leishmaniasis was undertaken and further structural analogs were synthesized for antileishmanial screening. Compound 1 was highly permeable in intestinal PAMPA model (31 x 10(-6) cm/s) and was moderately bound to mouse and human plasma proteins (% bound 85-95%), its blood to plasma concentration ratio was less than 1, but the compound was unstable in blood. Compound 1 was found to have no CYP450 liability with CYP2C9, 2C19, 2D6 and 3A4. It showed inhibition with CYP1A2 with an IC50 value of 0.50 mu M. Analogs of 1 were synthesized and subsequently characterized for in vitro activity against the intracellular form of Leishmania donovani. Resulting quinolines were found to have similar efficacy as 1 against the parasite. Compounds 8b and 8f were found to be the most active with IC50 values of 0.84 mu M and 0.17 mu M, respectively compared to 0.22 mu M for compound 1. Of all the analogs tested, 8d was stable in hamster, mouse and human liver microsomes but lost the efficacy with an IC50 of 6.42 mu M. Based on the in vitro efficacy and DMPK profile, compounds 8b and 8f seem the best candidates to be screened in further assays. (C) 2014 Elsevier Ltd. All rights reserved.