4-methyl-6-amino-8-[5'-O-(phenylphosphoryl (P->N)-L-valine methyl ester)-2',3'-O-dilevylinyl-β-D-ribofuranosyl]pyrrolo[4,3,2-d]pyrimidino[4,5-c]pyridazine | 1065474-61-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-methyl-6-amino-8-[5'-O-(phenylphosphoryl (P->N)-L-valine methyl ester)-2',3'-O-dilevylinyl-β-D-ribofuranosyl]pyrrolo[4,3,2-d]pyrimidino[4,5-c]pyridazine
• 英文别名: 2',3'-O-dilev-[6-amino-4-methyl-8-(β-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine]-5'-[phenyl methoxy-L-valyl]-phosphate；methyl (2S)-2-[[[(2R,3R,4R,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)-3,4-bis(4-oxopentanoyloxy)oxolan-2-yl]methoxy-phenoxyphosphoryl]amino]-3-methylbutanoate
• CAS: 1065474-61-4
• 化学式: C₃₅H₄₄N₇O₁₂P
• 分子量: 785.748
• InChiKey: KNIQALIXBATTMZ-SGCOIQOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  55
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  242
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  4-methyl-6-amino-8-[5'-O-(phenylphosphoryl (P->N)-L-valine methyl ester)-2',3'-O-dilevylinyl-β-D-ribofuranosyl]pyrrolo[4,3,2-d]pyrimidino[4,5-c]pyridazine 在 吡啶 、 溶剂黄146 、 肼 作用下， 反应 0.17h， 生成 4-methyl-6-amino-8-[5'-O-(phenylphosphoryl (P->N)-L-methyl ester valine)-β-D-ribofuranosyl]pyrrolo[4,3,2-d]pyrimidino[4,5-c]pyridazine
  参考文献：
  名称：

  WO2008/121941

  摘要：

  公开号：
• 作为产物：
  描述：

  曲西瑞宾 在 N-甲基咪唑 、 2,2-二羟甲基丙酸 、 四丁基氟化铵 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 4-methyl-6-amino-8-[5'-O-(phenylphosphoryl (P->N)-L-valine methyl ester)-2',3'-O-dilevylinyl-β-D-ribofuranosyl]pyrrolo[4,3,2-d]pyrimidino[4,5-c]pyridazine
  参考文献：
  名称：

  Expedient Total Synthesis of Triciribine and Its Prodrugs

  摘要：

  Triciribine (TCN, 1) and its monophosphate (TCNP, 2) are tricyclic nucleotide derivatives that have potential antineoplastic activity. Triciribine inhibits the phosphorylation, activation, and signaling of Akt-1, -2, and -3, which may result in the inhibition of Akt-expressing tumor cell proliferation. Both TCN and TCNP have very low bioavailability, and the development of both drugs as intravenous (IV) treatments was halted because of the toxicity induced by the high doses needed for their use as general cytotoxic agents. This publication describes an expedient and straightforward total synthesis of amino acid prodrugs (3, 4) of TCN and TCNP. In our study, both the prodrugs significant improved the plasma exposure of the parent drugs and the prodrugs.

  DOI：

  10.1080/00397911.2010.524342

文献信息

• Expedient Total Synthesis of Triciribine and Its Prodrugs
  作者：Wei Shen、Jae-Seung Kim、John Hilfinger

  DOI：10.1080/00397911.2010.524342

  日期：2012.2.1

  Triciribine (TCN, 1) and its monophosphate (TCNP, 2) are tricyclic nucleotide derivatives that have potential antineoplastic activity. Triciribine inhibits the phosphorylation, activation, and signaling of Akt-1, -2, and -3, which may result in the inhibition of Akt-expressing tumor cell proliferation. Both TCN and TCNP have very low bioavailability, and the development of both drugs as intravenous (IV) treatments was halted because of the toxicity induced by the high doses needed for their use as general cytotoxic agents. This publication describes an expedient and straightforward total synthesis of amino acid prodrugs (3, 4) of TCN and TCNP. In our study, both the prodrugs significant improved the plasma exposure of the parent drugs and the prodrugs.
• WO2008/121941
  申请人：——

  公开号：——

  公开（公告）日：——