4-(1-methylhydrazino)-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine | 699011-59-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-(1-methylhydrazino)-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 5-cyano-4-(1-methylhydrazino)-7-[2,3,5-tri-O-benzoyl-β-D-ribofuranosyl]pyrrolo[2,3-d]pyrimidine；[(2R,3R,4R,5R)-5-[4-[amino(methyl)amino]-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 699011-59-1
• 化学式: C₃₄H₂₈N₆O₇
• 分子量: 632.632
• InChiKey: HUVNVGZXBLWELK-QWOIFIOOSA-N

物化性质

• 熔点：
  168-170 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  830.3±65.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  172
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4-(1-methylhydrazino)-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 19.0h， 生成 曲西瑞宾
  参考文献：
  名称：

  Triciribine 的改进全合成：具有抗肿瘤和抗病毒特性的三环核苷

  摘要：

  我们描述了从 4-氨基-6-溴-5-氰基吡咯并[2,3-d]嘧啶开始，高效全合成曲西瑞宾，一种具有抗肿瘤和抗病毒特性的三环核苷。†为了纪念和庆祝 Leroy B. Townsend 教授 70 岁生日。

  DOI：

  10.1081/ncn-120027815
• 作为产物：
  描述：

  4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶 在 四(三苯基膦)钯 、 N,O-双三甲硅基乙酰胺 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.33h， 生成 4-(1-methylhydrazino)-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine
  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

• Synthesis of
  申请人：The United States of America as represented by the Department of Health,

  公开号：US04123524A1

  公开（公告）日：1978-10-31

  The compound 6-amino-4-methyl-8-(.beta.-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c ]pyridazines-5'-phosphate (a nucleotide) as a new compound and its method of synthesis by phosphorylation of the known 6-amino-4-methyl-8-(.beta.-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c ]pyridazine (a nucleoside). The 5'-phosphate ester has utility against L-1210 mouse leukemia and has superior solubility over the parent compound which gives it a broader use pattern relative to dosage. This novel nucleotide also shows advantage in utilization as to pH over, for example, the hydrochloride salt which gives in solution a pH of 4 and is too acid for use.

  化合物6-氨基-4-甲基-8-(β-D-核糖呋喃酰基)吡咯并[4,3,2-de]嘧啶并[4,5-c]吡啶嘧啶酸酯（一种核苷酸）作为一种新化合物，其合成方法是通过对已知的6-氨基-4-甲基-8-(β-D-核糖呋喃基)吡咯并[4,3,2-de]嘧啶并[4,5-c]吡啶嘧啶（一种核苷）进行磷酸化而得到。5'-磷酸酯对L-1210小鼠白血病具有治疗作用，并且相对于剂量而言，其溶解度优于母体化合物，从而使其具有更广泛的用途。这种新型核苷酸在pH值的利用方面也具有优势，例如，与盐酸盐相比，后者在溶液中的pH值为4，过于酸性，不能使用。
• Synth. Commun. 2012, 42, 358-374
  作者：

  DOI：——

  日期：——
• 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.
• An Improved Total Synthesis of Triciribine: A Tricyclic Nucleoside with Antineoplastic and Antiviral Properties
  作者：Anthony R. Porcari、Leroy B. Townsend

  DOI：10.1081/ncn-120027815

  日期：2004.1.1

  We describe an efficient total synthesis of triciribine, a tricyclic nucleoside with antineoplastic and antiviral properties, starting from 4‐amino‐6‐bromo‐5‐cyanopyrrolo[2,3‐d]pyrimidine. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

  我们描述了从 4-氨基-6-溴-5-氰基吡咯并[2,3-d]嘧啶开始，高效全合成曲西瑞宾，一种具有抗肿瘤和抗病毒特性的三环核苷。†为了纪念和庆祝 Leroy B. Townsend 教授 70 岁生日。