2-(dimethylamino)-7-amino-9H-thioxanthen-9-one | 1158967-53-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫色烯
• 英文名称: 2-(dimethylamino)-7-amino-9H-thioxanthen-9-one
• 英文别名: 3-Amino-6-(dimethylamino)thioxanthen-9-one
• CAS: 1158967-53-3
• 化学式: C₁₅H₁₄N₂OS
• 分子量: 270.355
• InChiKey: FLFJFWIFNDPEBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(dimethylamino)-7-amino-9H-thioxanthen-9-one 、 三苯基氯甲烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以75%的产率得到3-(dimethylamino)-6-(tritylamino)-9H-thioxanthen-9-one
  参考文献：
  名称：

  Rhodamine Inhibitors of P-Glycoprotein: An Amide/Thioamide “Switch” for ATPase Activity

  摘要：

  We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K-M of 0.087 mu M in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC50's of similar to 2 mu M in MDCKII-MDR1 cells.

  DOI：

  10.1021/jm900253g
• 作为产物：
  描述：

  3-nitro-6-(dimethylamino)-9H-thioxanthen-9-one 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以81%的产率得到2-(dimethylamino)-7-amino-9H-thioxanthen-9-one
  参考文献：
  名称：

  Rhodamine Inhibitors of P-Glycoprotein: An Amide/Thioamide “Switch” for ATPase Activity

  摘要：

  We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K-M of 0.087 mu M in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC50's of similar to 2 mu M in MDCKII-MDR1 cells.

  DOI：

  10.1021/jm900253g

文献信息

• Rhodamine Inhibitors of P-Glycoprotein: An Amide/Thioamide “Switch” for ATPase Activity
  作者：Michael K. Gannon、Jason J. Holt、Stephanie M. Bennett、Bryan R. Wetzel、Tip W. Loo、M. Claire Bartlett、David M. Clarke、Geri A. Sawada、J. William Higgins、Gregory Tombline、Thomas J. Raub、Michael R. Detty

  DOI：10.1021/jm900253g

  日期：2009.5.28

  We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K-M of 0.087 mu M in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC50's of similar to 2 mu M in MDCKII-MDR1 cells.