4H-2,6-bis(4-morpholinophenyl)-thiopyran-4-one | 1093845-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4H-2,6-bis(4-morpholinophenyl)-thiopyran-4-one
• CAS: 1093845-66-9
• 化学式: C₂₅H₂₆N₂O₃S
• 分子量: 434.559
• InChiKey: AOJHFAUCBMYCFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.12
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  42.01
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4H-2,6-bis(4-morpholinophenyl)-thiopyran-4-one 、 苯基溴化镁 在 hexafluorophosphoric acid 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以91%的产率得到
  参考文献：
  名称：

  Chalcogenopyrylium dyes as inhibitors/modulators of P-glycoprotein in multidrug-resistant cells

  摘要：

  A series of chalcogenopyrylium dyes were evaluated as modulators/inhibitors of P-glycoprotein (Pgp). Their ability to inhibit verapamil (VER)-dependent ATPase activity (IC50 values) in lipid-activated, mouse Cys-less mdr3 Pgp was determined. Their ability to promote calcein-AM (CAM) uptake in MDCKII-MDR1 cells and their capacity to be transported by Pgp in monolayers of MDCKII-MDR1 cells were also evaluated. The chalcogenopyrylium dyes promoted CAM uptake with values of EC50 between 5 x 10 (6) and 3.5 x 10 (5) M and 7 of the 9 dyes examined in transport studies were substrates for Pgp with efflux ratios (P-BA/AB) between 14 and 390. Binding of three compounds (1-S, 3-S, and 4-S) to Pgp was also assessed by fluorescence. These three thiopyrylium dyes showed increased fluorescence upon binding to Pgp, giving apparent binding constants, K-app, on the order of 10 (7) to 10 (6) M. Compound 8-Te was particularly intriguing since it appeared to influence Pgp at low micromolar concentrations as evidenced by its influence on VER-stimulated ATPase activity (IC50 of 1.2 x 10 (6) M), CAM uptake (EC50 of 5.4 x 10 (6) M), as well as [H-3]-vinblastine transport by Pgp in cells (IC50 of 4.3 x 10 (6) M) and within inside-out membrane vesicles (IC50 of 9.6 x 10 (6) M). Yet, Pgp did not influence the distribution of 8-Te in MDCKII-MDR1 monolayers suggesting that 8-Te may bind to an allosteric site. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.065
• 作为产物：
  描述：

  1,5-bis(4-morpholinophenyl)-1,4-pentadiyn-3-one 在 sodium ethanolate 、 sodium sulfide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以80%的产率得到4H-2,6-bis(4-morpholinophenyl)-thiopyran-4-one
  参考文献：
  名称：

  Chalcogenopyrylium dyes as inhibitors/modulators of P-glycoprotein in multidrug-resistant cells

  摘要：

  A series of chalcogenopyrylium dyes were evaluated as modulators/inhibitors of P-glycoprotein (Pgp). Their ability to inhibit verapamil (VER)-dependent ATPase activity (IC50 values) in lipid-activated, mouse Cys-less mdr3 Pgp was determined. Their ability to promote calcein-AM (CAM) uptake in MDCKII-MDR1 cells and their capacity to be transported by Pgp in monolayers of MDCKII-MDR1 cells were also evaluated. The chalcogenopyrylium dyes promoted CAM uptake with values of EC50 between 5 x 10 (6) and 3.5 x 10 (5) M and 7 of the 9 dyes examined in transport studies were substrates for Pgp with efflux ratios (P-BA/AB) between 14 and 390. Binding of three compounds (1-S, 3-S, and 4-S) to Pgp was also assessed by fluorescence. These three thiopyrylium dyes showed increased fluorescence upon binding to Pgp, giving apparent binding constants, K-app, on the order of 10 (7) to 10 (6) M. Compound 8-Te was particularly intriguing since it appeared to influence Pgp at low micromolar concentrations as evidenced by its influence on VER-stimulated ATPase activity (IC50 of 1.2 x 10 (6) M), CAM uptake (EC50 of 5.4 x 10 (6) M), as well as [H-3]-vinblastine transport by Pgp in cells (IC50 of 4.3 x 10 (6) M) and within inside-out membrane vesicles (IC50 of 9.6 x 10 (6) M). Yet, Pgp did not influence the distribution of 8-Te in MDCKII-MDR1 monolayers suggesting that 8-Te may bind to an allosteric site. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.065