2-[(2S,5R)-5-(3-Amino-5-methyl-5H-1,4,5,6,8-pentaaza-acenaphthylen-1-yl)-2,5-dihydro-furan-2-ylmethoxy]-2,5,5-trimethyl-[1,3]dioxolan-4-one | 286015-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 2-[(2S,5R)-5-(3-Amino-5-methyl-5H-1,4,5,6,8-pentaaza-acenaphthylen-1-yl)-2,5-dihydro-furan-2-ylmethoxy]-2,5,5-trimethyl-[1,3]dioxolan-4-one
• 英文别名: 2-[[(2S,5R)-5-(5-amino-7-methyl-2,6,7,9,11-pentazatricyclo[6.3.1.04,12]dodeca-1(12),3,5,8,10-pentaen-2-yl)-2,5-dihydrofuran-2-yl]methoxy]-2,5,5-trimethyl-1,3-dioxolan-4-one
• CAS: 286015-14-3
• 化学式: C₁₉H₂₂N₆O₅
• 分子量: 414.421
• InChiKey: HLXHGTZAUMQEQS-WIYWQTCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[(2S,5R)-5-(3-Amino-5-methyl-5H-1,4,5,6,8-pentaaza-acenaphthylen-1-yl)-2,5-dihydro-furan-2-ylmethoxy]-2,5,5-trimethyl-[1,3]dioxolan-4-one 在 氨 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以80%的产率得到2',3'-d4TCN
  参考文献：
  名称：

  Deoxy Sugar Analogues of Triciribine:  Correlation of Antiviral and Antiproliferative Activity with Intracellular Phosphorylation

  摘要：

  Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and antineoplastic activity at low micromolar or submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore requirements for the number of hydroxyl groups on the ribosyl moiety for biological activity. 2'-Deoxytriciribine (2'-dTCN), 3'-deoxytriciribine (3'-dTCN), 2',3'-epoxytriciribine (2',3'-epoxyTCN), 2',3'-dideoxy-2',3'-didehydrotriciribine (2',3'-d4TCN), and 2',3'-dideoxytriciribine (2',3'-ddTCN) were synthesized and evaluated for activity against human immunodeficiency virus (HIV-1), herpes simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV). Antiproliferative activity of the compounds also was tested in murine L1210 cells and three human tumor cell lines. All compounds were either less active than TCN and TCN-P or inactive at the highest concentration tested (100 mu M) in both antiviral and antiproliferative assays. Reverse-phase HPLC of extracts from uninfected cells treated with the deoxytriciribine analogues only detected the conversion of 3'-dTCN and 2',3'-ddTCN to their respective monophosphates. Therefore, either the deoxytriciribine analogues were not transported across the cell membrane or, more likely, they were not substrates for a nucleoside kinase or phosphotransferase. We have concluded that the hydroxyl groups on the ribosyl ring system of TCN and TCN-P must be intact in order to obtain significant antiviral and antineoplastic activity.

  DOI：

  10.1021/jm990205m
• 作为产物：
  描述：

  8-[2-O-acetyl-3-bromo-3-deoxy-5-O-(2,3,5-trimethyl-1,3-dioxolan-4-one-2-yl)-β-D-xylofuranosyl]-6-amino-4-methylpyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine 在 铜 、 溶剂黄146 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以71%的产率得到2-[(2S,5R)-5-(3-Amino-5-methyl-5H-1,4,5,6,8-pentaaza-acenaphthylen-1-yl)-2,5-dihydro-furan-2-ylmethoxy]-2,5,5-trimethyl-[1,3]dioxolan-4-one
  参考文献：
  名称：

  Deoxy Sugar Analogues of Triciribine:  Correlation of Antiviral and Antiproliferative Activity with Intracellular Phosphorylation

  摘要：

  Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and antineoplastic activity at low micromolar or submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore requirements for the number of hydroxyl groups on the ribosyl moiety for biological activity. 2'-Deoxytriciribine (2'-dTCN), 3'-deoxytriciribine (3'-dTCN), 2',3'-epoxytriciribine (2',3'-epoxyTCN), 2',3'-dideoxy-2',3'-didehydrotriciribine (2',3'-d4TCN), and 2',3'-dideoxytriciribine (2',3'-ddTCN) were synthesized and evaluated for activity against human immunodeficiency virus (HIV-1), herpes simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV). Antiproliferative activity of the compounds also was tested in murine L1210 cells and three human tumor cell lines. All compounds were either less active than TCN and TCN-P or inactive at the highest concentration tested (100 mu M) in both antiviral and antiproliferative assays. Reverse-phase HPLC of extracts from uninfected cells treated with the deoxytriciribine analogues only detected the conversion of 3'-dTCN and 2',3'-ddTCN to their respective monophosphates. Therefore, either the deoxytriciribine analogues were not transported across the cell membrane or, more likely, they were not substrates for a nucleoside kinase or phosphotransferase. We have concluded that the hydroxyl groups on the ribosyl ring system of TCN and TCN-P must be intact in order to obtain significant antiviral and antineoplastic activity.

  DOI：

  10.1021/jm990205m

文献信息

• Deoxy Sugar Analogues of Triciribine:  Correlation of Antiviral and Antiproliferative Activity with Intracellular Phosphorylation
  作者：Anthony R. Porcari、Roger G. Ptak、Katherine Z. Borysko、Julie M. Breitenbach、Sauro Vittori、Linda L. Wotring、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm990205m

  日期：2000.6.1

  Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and antineoplastic activity at low micromolar or submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore requirements for the number of hydroxyl groups on the ribosyl moiety for biological activity. 2'-Deoxytriciribine (2'-dTCN), 3'-deoxytriciribine (3'-dTCN), 2',3'-epoxytriciribine (2',3'-epoxyTCN), 2',3'-dideoxy-2',3'-didehydrotriciribine (2',3'-d4TCN), and 2',3'-dideoxytriciribine (2',3'-ddTCN) were synthesized and evaluated for activity against human immunodeficiency virus (HIV-1), herpes simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV). Antiproliferative activity of the compounds also was tested in murine L1210 cells and three human tumor cell lines. All compounds were either less active than TCN and TCN-P or inactive at the highest concentration tested (100 mu M) in both antiviral and antiproliferative assays. Reverse-phase HPLC of extracts from uninfected cells treated with the deoxytriciribine analogues only detected the conversion of 3'-dTCN and 2',3'-ddTCN to their respective monophosphates. Therefore, either the deoxytriciribine analogues were not transported across the cell membrane or, more likely, they were not substrates for a nucleoside kinase or phosphotransferase. We have concluded that the hydroxyl groups on the ribosyl ring system of TCN and TCN-P must be intact in order to obtain significant antiviral and antineoplastic activity.