6-(heptyloxy)-9H-purine | 62134-32-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-(heptyloxy)-9H-purine
• 英文别名: 6-(Heptyloxy)-7H-purine；6-heptoxy-7H-purine
• CAS: 62134-32-1
• 化学式: C₁₂H₁₈N₄O
• 分子量: 234.301
• InChiKey: ATKMTEHDPYMKBD-UHFFFAOYSA-N

物化性质

• 沸点：
  360.2±52.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2',3'-二脱氧胸苷 、 6-(heptyloxy)-9H-purine 在 对硝基苯酚 、 potassium phosphate buffer containing 0.004percent potassium azide (buffer A) 、 TPase 作用下， 反应 24.0h， 以36%的产率得到6-(heptyloxy)-9-<(2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl>-9H-purine
  参考文献：
  名称：

  Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus

  摘要：

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.

  DOI：

  10.1021/jm00055a009
• 作为产物：
  描述：

  正庚醇 、 6-氯嘌呤 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 6-(heptyloxy)-9H-purine
  参考文献：
  名称：

  Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus

  摘要：

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.

  DOI：

  10.1021/jm00055a009

文献信息

• Photographic element containing a DIR coupler
  申请人：Eastman Kodak Company

  公开号：US06238855B1

  公开（公告）日：2001-05-29

  A photographic element comprising a support bearing one or more silver halide emulsions at least one of which comprises at least 50% silver chloride in association with one or more image dye-forming couplers and one or more DI(A)R couplers of formulae I or II: wherein: TIME is a timing group and R1, R2, Z, n, and j are as defined in the specification, wherein the DI(A)R coupler(s) in association with an emulsion comprising at least 50% silver chloride comprise at least about 25% to about 90% of the total amount of coupler in association with that emulsion and the total amount of coupler is the sum of the number of moles of image coupler(s) and the number of moles of the DI(A)R couplers in association with that emulsion.

  一种摄影元素，包括一种支撑体，该支撑体承载着至少一种银卤化物乳剂，其中至少一种乳剂包括至少50％的氯化银，并与一种或多种图像染料形成偶联剂和一种或多种DI（A）R偶联剂的结合物相结合，其中：TIME是计时基团，R1、R2、Z、n和j如规范中所定义，其中与至少50％的氯化银的乳剂一起使用的DI（A）R偶联剂占该乳剂中偶联剂总量的至少约25％至约90％，偶联剂的总量是图像偶联剂的摩尔数和DI（A）R偶联剂的摩尔数之和。
• Photographic element containing a dir coupler
  申请人：EASTMAN KODAK COMPANY

  公开号：EP1014184B1

  公开（公告）日：2003-02-26
• US6238855B1
  申请人：——

  公开号：US6238855B1

  公开（公告）日：2001-05-29
• Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus
  作者：Charlene L. Burns、Marty H. St. Clair、Lloyd W. Frick、Thomas Spector、Devron R. Averett、Michael L. English、Timothy J. Holmes、Thomas A. Krenitsky、George W. Koszalka

  DOI：10.1021/jm00055a009

  日期：1993.2

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.