1-(2-deoxy-β-D-ribofuranosyl)-7-iodoisocarbostyril | 374694-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(2-deoxy-β-D-ribofuranosyl)-7-iodoisocarbostyril
• 英文别名: 2-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-iodoisoquinolin-1-one
• CAS: 374694-91-4
• 化学式: C₁₄H₁₄INO₄
• 分子量: 387.174
• InChiKey: DDWYVBDNOFULRS-YNEHKIRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-β-D-ribofuranosyl)-7-iodoisocarbostyril 在 bis-triphenylphosphine-palladium(II) chloride 一氯化碘 作用下， 以 乙腈 为溶剂， 反应 24.25h， 生成 1-(2-deoxy-β-D-ribofuranosyl)-7-(E)-(2-iodovinyl)isocarbostyril
  参考文献：
  名称：

  SYNTHESIS OF UNNATURAL 7-SUBSTITUTED-1-(2-DEOXY-β-D-RIBOFURANOSYL)ISOCARBOSTYRILS^†: “THYMINE REPLACEMENT” ANALOGS OF DEOXYTHYMIDINE FOR EVALUATION AS ANTIVIRAL AND ANTICANCER AGENTS

  摘要：

  A group of unnatural 1-(2-deoxy-beta -D-ribofuranosyl)isocarbostyrils having a variety of C-7 substituents [H, 4,7-(NO2)(2), I, CF3, CN, (E)-CH=CH-I, -C drop CH, -C dropC-I, -C dropC-Br, -C dropC-Me], designed as nucleoside mimics, were synthesized for evaluation as anticancer and antiviral agents. This class of compounds exhibited weak cytotoxicity in a MTT assay (CC50 = 10(-3) to 10(-5) M range) with the 4,7-dinitro derivative being the most cytotoxic, relative to thymidine (CC50=10(-3) to 10(-5) M range), against a variety of cancer cell lines. The 4,7-dinitro, 7-I and 7-C drop CH compounds exhibited similar cytotoxicity against nontransfected (KBALB, 143B), and HSV-1 TK+ gene transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type I (HSV-1) thymidine kinase gene (TK+). This observation indicates that these compounds are not substrates for HSV type-1 TK, and are therefore unlikely to be useful in gene therapy based on the HSV gene therapy paradigm.

  DOI：

  10.1081/ncn-100105246
• 作为产物：
  描述：

  1-氯-2-脱氧-3,5-二-O-对氯苯甲酰基-D-核糖 在 N,O-双三甲硅基乙酰胺 、 sodium methylate 、 一氯化碘 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 1-(2-deoxy-β-D-ribofuranosyl)-7-iodoisocarbostyril
  参考文献：
  名称：

  SYNTHESIS OF UNNATURAL 7-SUBSTITUTED-1-(2-DEOXY-β-D-RIBOFURANOSYL)ISOCARBOSTYRILS^†: “THYMINE REPLACEMENT” ANALOGS OF DEOXYTHYMIDINE FOR EVALUATION AS ANTIVIRAL AND ANTICANCER AGENTS

  摘要：

  A group of unnatural 1-(2-deoxy-beta -D-ribofuranosyl)isocarbostyrils having a variety of C-7 substituents [H, 4,7-(NO2)(2), I, CF3, CN, (E)-CH=CH-I, -C drop CH, -C dropC-I, -C dropC-Br, -C dropC-Me], designed as nucleoside mimics, were synthesized for evaluation as anticancer and antiviral agents. This class of compounds exhibited weak cytotoxicity in a MTT assay (CC50 = 10(-3) to 10(-5) M range) with the 4,7-dinitro derivative being the most cytotoxic, relative to thymidine (CC50=10(-3) to 10(-5) M range), against a variety of cancer cell lines. The 4,7-dinitro, 7-I and 7-C drop CH compounds exhibited similar cytotoxicity against nontransfected (KBALB, 143B), and HSV-1 TK+ gene transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type I (HSV-1) thymidine kinase gene (TK+). This observation indicates that these compounds are not substrates for HSV type-1 TK, and are therefore unlikely to be useful in gene therapy based on the HSV gene therapy paradigm.

  DOI：

  10.1081/ncn-100105246

文献信息

• Phosphorylation of Isocarbostyril‐ and Difluorophenyl‐Nucleoside Thymidine Mimics by the Human Deoxynucleoside Kinases
  作者：Ashraf Said Al‐Madhoun、Staffan Eriksson、Zhi‐Xian Wang、Ebrahim Naimi、Edward E. Knaus、Leonard I. Wiebe

  DOI：10.1081/ncn-200040634

  日期：2004.1.12

  The thymidine mimics isocarbostyril nucleosides and difluorophenyl nucleosides were tested as deoxynucleoside kinase substrates using recombinant human cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK), and mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK). The isocarbostyril nucleoside compound 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril (EN1) was a poor substrate with all the enzymes. The phosphorylation rates of EN1 with TKI and TK2 were <1% relative to Thd, where as the phosphorylation rates for EN1 were 1.4% and 1.1% with dCK and dGK relative to dCyd and dGuo, respectively. The analogue 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril (EN2) showed poor relative-phosphorylation efficiencies (k(cat)/Kappa(m).) with both TK1 and dGK, but not with TK2. The k(cat)/Kappa(m) value for EN2 with TK2 was 12.6% relative to that for Thd. Of the difluorophenyl nucleosides, 5-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluorotoluene (JW1) and 1-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluoro-5-iodobenzene (JW2) were substrates for TK1 with phosphorylation efficiencies of about 5% relative to that for Thd. Both analogues were considerably more efficient substrates for TK2, with k(cat)/Kappa(m). values of 45% relative to that for Thd. 2,5-Difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline (JW5), a L-nucleoside mimic, was phosphorylated up to 15% as efficiently as deoxycytidine by dCK. These data provide a possible explanation for the previously reported lack of cytotoxicity of the isocarbostyril- and difluorophenyl nucleosides, but potential mitochondrial effects of EN2, JW1 and JW2 should be further investigated.