4-amino-5-cyano-7-<3,5-O-<1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl>-β-D-ribofuranosyl>pyrrolo<2,3-d>pyrimidine | 85335-79-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-5-cyano-7-<3,5-O-<1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl>-β-D-ribofuranosyl>pyrrolo<2,3-d>pyrimidine
• 英文别名: 3',5'-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl)-toyocamycin；4-amino-7-((6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile；4-amino-5-cyano-7-[3,5-O-(1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl)-β-D-ribofuranosyl]pyrrolo[2,3-d]pyrimidine；7-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-4-aminopyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 85335-79-1
• 化学式: C₂₄H₃₉N₅O₅Si₂
• 分子量: 533.775
• InChiKey: FSPBREWRCSRMKV-UMCMBGNQSA-N

物化性质

• 沸点：
  617.4±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-amino-5-cyano-7-<3,5-O-<1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl>-β-D-ribofuranosyl>pyrrolo<2,3-d>pyrimidine 在 4-二甲氨基吡啶 、 ammonium hydroxide 、 四丁基氟化铵 、 双氧水 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 1,2-二氯乙烷 为溶剂， 反应 15.5h， 生成 4-amino-7-(2-deoxy-2-iodo-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine-5-carboxamide
  参考文献：
  名称：

  Arabinofuranosylpyrrolo[2,3-d]pyrimidines as potential agents for human cytomegalovirus infections

  摘要：

  Protection of the 3'- and 5'-hydroxyl groups of the nucleoside antibiotic toyocamycin (1) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane was followed by (trifluoromethyl)sulfonylation of the 2'-hydroxyl group. A displacement of the resulting triflate ester moiety with lithium chloride, lithium bromide, sodium iodide, and lithium azide in hexamethylphosphoramide was followed by a removal of the disilyl moiety with tetra-n-butylammonium fluoride to afford the appropriate (2'-deoxy-2'-substituted-arabinofuranosyl)toyocamycin analogues 6a-d. Hydrolysis of the carbonitrile moieties of 6a-d with hydrogen peroxide gave the corresponding sangivamycin analogues (7a-d). A reduction of the azido moiety of 6a and 7a with 1,3-propanedithiol furnished the corresponding amino derivatives (6e and 7e). The antiproliferative activity of 6a-e and 7a-e was evaluated in L1210 cell cultures. None of these compounds caused significant inhibition of cell growth. Evaluation of these compounds for antiviral activity showed that all the toyocamycin analogues were active against human CMV, but of the sangivamycin analogues, only (2'-deoxy-2'-azidoarabinosyl)sangivamycin (7a) was active against this virus. None of the compounds were active against HSV-1 or HSV-2. (2'-Deoxy-2'-aminoarabinofuranosyl)toyocamycin (6e) was studied more extensively and showed some separation between antiviral activity and cytotoxicity as measured by effects on DNA synthesis, cell growth, and cell-plating efficiency. Although 6e also was active against murine CMV in vitro, it was not active against this virus in infected mice. We conclude that arabinosylpyrrolopyrimidines have potential as antivirals, but no members of the current series are potent enough to show significant activity in vivo.

  DOI：

  10.1021/jm00174a011
• 作为产物：
  描述：

  diisopropylsilanol 在 吡啶 、 phosphorus pentoxide 、 氯 作用下， 以 四氯化碳 为溶剂， 反应 3.5h， 生成 4-amino-5-cyano-7-<3,5-O-<1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl>-β-D-ribofuranosyl>pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Nucleic acid related compounds. 42. A general procedure for the efficient deoxygenation of secondary alcohols. Regiospecific and stereoselective conversion of ribonucleosides to 2'-deoxynucleosides

  摘要：

  DOI：

  10.1021/ja00350a052

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION<br/>[FR] COMPOSÉS, COMPOSITIONS, ET PROCÉDÉS POUR LE TRAITEMENT D'UNE INFECTION VIRALE
  申请人：CHIMERIX INC

  公开号：WO2010135520A1

  公开（公告）日：2010-11-25

  The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).

  本发明描述了式I和式II的化合物以及治疗病毒感染的方法，例如黄病毒科病毒感染，包括丙型肝炎病毒感染（HCV）。
• 2' And 3'-ketonucleosides and their arabino and xylo reduction products
  作者：Fritz Hansske、Danuta Madej、Morris J. Robins

  DOI：10.1016/0040-4020(84)85111-x

  日期：1984.1

  A number of 2',5'- or 3',5'-diprotected ribonucleosides and 5'-protected 2'- or 3'-deoxy-β-D-erythro-pentofuranosyl nucleosides have been oxidized to the corresponding 3' or 2'-ketonucleoside derivatives using chromium trioxide/pyridine/acetic anhydride or dimethyl sulfoxide/ acetic anhydride. Reduction of the carbonyl functions with sodium borohydride gave the inverted arabino, xylo, or deoxy-threo

  许多2'，5'-或3'，5'-双保护核糖核苷和5'-保护的2'-或3'-脱氧-β-D-赤型-戊呋喃糖基核苷已被氧化为相应的3'或2使用三氧化铬/吡啶/乙酸酐或二甲基亚砜/乙酸酐的'-酮核苷衍生物。用硼氢化钠还原羰基官能团，可以通过在糖环的受阻较少的α面上进行攻击，使倒位的阿拉伯糖，木糖或脱氧苏糖异构体成为主要产物。通过证明已经发生了原始羟基的完全氧化，使用硼氢化氘化钠的平行还原证实了差向异构体比率。氘标记还有助于进行NMR 频谱分配。
• COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION
  申请人：Almond Merrick

  公开号：US20100297079A1

  公开（公告）日：2010-11-25

  The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).

  本发明描述了I和II式化合物以及治疗病毒感染的方法，例如Flaviviridae病毒感染，包括丙型肝炎（HCV）感染。
• KRAWCZYK, STEVEN H.;BERNIER-RODRIGUEZ, MARTHA;NASSIRI, REZA M.;KERN, EARL+, J. MED. CHEM., 33,(1990) N2, C. 3160-3169
  作者：KRAWCZYK, STEVEN H.、BERNIER-RODRIGUEZ, MARTHA、NASSIRI, REZA M.、KERN, EARL+

  DOI：——

  日期：——
• Nucleic acid related compounds. 42. A general procedure for the efficient deoxygenation of secondary alcohols. Regiospecific and stereoselective conversion of ribonucleosides to 2'-deoxynucleosides
  作者：Morris J. Robins、John S. Wilson、Fritz Hansske

  DOI：10.1021/ja00350a052

  日期：1983.6