3,6-bis(tritylamino)-9H-thioxanthen-9-one | 1158967-63-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3,6-bis(tritylamino)-9H-thioxanthen-9-one
• 英文别名: 3,6-Bis(tritylamino)thioxanthen-9-one
• CAS: 1158967-63-5
• 化学式: C₅₁H₃₈N₂OS
• 分子量: 726.942
• InChiKey: QENISFMCXOOVQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.8
• 重原子数：
  55
• 可旋转键数：
  10
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,6-bis(tritylamino)-9H-thioxanthen-9-one 、 苯基溴化镁 在 hexafluorophosphoric acid 作用下， 以 乙醚 、 水 、 溶剂黄146 为溶剂， 以46%的产率得到3,6-diamino-9-phenylthioxanthylium hexafluorophosphate
  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：

  3,6-diamino-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59%的产率得到3,6-bis(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

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.