1,5-bis(4-morpholinophenyl)-1,4-pentadiyn-3-one | 477941-59-6

• 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: 1,5-bis(4-morpholinophenyl)-1,4-pentadiyn-3-one
• 英文别名: 1,5-Bis(4-morpholin-4-ylphenyl)penta-1,4-diyn-3-one
• CAS: 477941-59-6
• 化学式: C₂₅H₂₄N₂O₃
• 分子量: 400.477
• InChiKey: DBKRPBWLVUJSPC-UHFFFAOYSA-N

物化性质

• 沸点：
  618.5±65.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-(4-ethynylphenyl)morpholine 在 manganese(IV) oxide 、 正丁基锂 作用下， 生成 1,5-bis(4-morpholinophenyl)-1,4-pentadiyn-3-one
  参考文献：
  名称：

  In Vitro Photodynamic Properties of Chalcogenopyrylium Analogues of the Thiopyrylium Antitumor Agent AA1

  摘要：

  Several series of chalcogenopyrylium dyes were prepared with one or two 4-anilino substituents at the 2- and 6-positions and with phenyl, 4-N,N-dimethylanilino, or 4-(N-morphilino)phenyl substituents at 2- and/or 4-positions. The dye series are all related in structure to AA1, a thiopyrylium dye that targets mitochondria. The chalcogenopyrylium. nuclei included sulfur, selenium, and tellurium at the 1-position. Key intermediates in the dye synthesis were the corresponding Delta-4H-chalcogenopyran-4-ones. All of the dyes of this study were evaluated for dark and phototoxicity toward Colo-26 cells in vitro. There was no correlation of dark toxicity with either the reduction potential of the chalcogenopyrylium dye or the n-octanol/water partition coefficient, log P. Several of the dyes of this study (thiopyrylium dyes 1-S and 13-S, selenopyrylium dyes 1-Se, 2-Se, 3-Se, 4-Se, 13-Se, 14-Se, and 27-Se, and telluropyrylium dye 13-Te) showed added phototoxicity upon irradiation. Dyes with the highest therapeutic ratio as measured by dark toxicity/phototoxicity (15 J cm(-2) of 360-800-nm light) had values of log P of 1.0-1.2. Studies of cytochrome c oxidase activity in whole R3230AC cells suggested that dyes I-S and 3-Se, with values of log P of 2.2 and 1.7, respectively, were localized in the mitochondria. Cytocrome c oxidase activity in whole cells was inhibited by 1-S and 3-Se in the dark. Chalcogenopyrylium dyes 2-Se, 4-Se, 13-Te, and 14-Se inhibited whole-cell cytochrome c oxidase activity only following irradiation, which suggests that these dyes relocalized to mitochondria following irradiation.

  DOI：

  10.1021/jm020260m

文献信息

• In Vitro Photodynamic Properties of Chalcogenopyrylium Analogues of the Thiopyrylium Antitumor Agent AA1
  作者：Nancy K. Brennan、Jonathan P. Hall、Sherry R. Davies、Sandra O. Gollnick、Allan R. Oseroff、Scott L. Gibson、Russell Hilf、Michael R. Detty

  DOI：10.1021/jm020260m

  日期：2002.11.1

  Several series of chalcogenopyrylium dyes were prepared with one or two 4-anilino substituents at the 2- and 6-positions and with phenyl, 4-N,N-dimethylanilino, or 4-(N-morphilino)phenyl substituents at 2- and/or 4-positions. The dye series are all related in structure to AA1, a thiopyrylium dye that targets mitochondria. The chalcogenopyrylium. nuclei included sulfur, selenium, and tellurium at the 1-position. Key intermediates in the dye synthesis were the corresponding Delta-4H-chalcogenopyran-4-ones. All of the dyes of this study were evaluated for dark and phototoxicity toward Colo-26 cells in vitro. There was no correlation of dark toxicity with either the reduction potential of the chalcogenopyrylium dye or the n-octanol/water partition coefficient, log P. Several of the dyes of this study (thiopyrylium dyes 1-S and 13-S, selenopyrylium dyes 1-Se, 2-Se, 3-Se, 4-Se, 13-Se, 14-Se, and 27-Se, and telluropyrylium dye 13-Te) showed added phototoxicity upon irradiation. Dyes with the highest therapeutic ratio as measured by dark toxicity/phototoxicity (15 J cm(-2) of 360-800-nm light) had values of log P of 1.0-1.2. Studies of cytochrome c oxidase activity in whole R3230AC cells suggested that dyes I-S and 3-Se, with values of log P of 2.2 and 1.7, respectively, were localized in the mitochondria. Cytocrome c oxidase activity in whole cells was inhibited by 1-S and 3-Se in the dark. Chalcogenopyrylium dyes 2-Se, 4-Se, 13-Te, and 14-Se inhibited whole-cell cytochrome c oxidase activity only following irradiation, which suggests that these dyes relocalized to mitochondria following irradiation.
• Chalcogenopyrylium dyes as inhibitors/modulators of P-glycoprotein in multidrug-resistant cells
  作者：Geri A. Sawada、Thomas J. Raub、J. William Higgins、Nancy K. Brennan、Teiah M. Moore、Gregory Tombline、Michael R. Detty

  DOI：10.1016/j.bmc.2008.09.065

  日期：2008.11

  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.