6-chloro-9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine | 109304-00-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-chloro-9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine
• 英文别名: [(2R,3R,4S,5R)-3-acetyloxy-5-(6-chloropurin-9-yl)-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 109304-00-9
• 化学式: C₁₉H₁₆ClFN₄O₅
• 分子量: 434.811
• InChiKey: SRNCCQXLHAOBKY-ZFHGCVPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105.43
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  6-chloro-9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine 在 咪唑 、 偶氮二异丁腈 、 (dimethylamido)pyridine 、 四丁基氟化铵 、 氨 、 三正丁基氢锡 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 106.18h， 生成 9-[(2R,3S,5S)-3-氟-5-(羟基甲基)四氢呋喃-2-基]-3H-嘌呤-6-酮
  参考文献：
  名称：

  Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV

  摘要：

  2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.

  DOI：

  10.1021/jm00165a015
• 作为产物：
  描述：

  1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose 在 4 A molecular sieve 、 氢溴酸 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 反应 16.0h， 生成 6-chloro-9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purine
  参考文献：
  名称：

  Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV

  摘要：

  2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.

  DOI：

  10.1021/jm00165a015

文献信息

• Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-.BETA.-D-arabinofuranosyl)-9H-purines and their biological activities.
  作者：Chung K. CHU、Jasenka MATULIC-ADAMIC、Jai-Tung HUANG、Ting-Chao CHOU、Joseph H. BURCHENAL、Jack J. FOX、Kyoichi A. WATANABE

  DOI：10.1248/cpb.37.336

  日期：——

  silyl procedure afforded the protected 2-acetamido-6-chloropurine nucleoside which served as the precursor for both the guanine and 6-thioguanine nucleosides (VI, 2'-F-ara-G and VII, 2'-F-ara-TG, respectively). Thus, alkaline hydrolysis of the precursor gave VI. Thiourea treatment prior to alkaline hydrolysis gave VII. The new nucleoside, 2'-F-ara-G (VI) is found to be selectively toxic to human T-cell

  合成了含有2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基部分的七个嘌呤核苷，并测试了它们的抗肿瘤活性。3-O-乙酰基-5-O-苯甲酰基-2-脱氧-2-氟-D-阿拉伯呋喃糖基溴化物（1）与N6-苯甲酰腺嘌呤在CH2Cl2中的直接缩合，然后将产物皂化，得到腺嘌呤核苷（I，2 -F-ara-A）。用HOAc中的NaNO 2脱除I，得到次黄嘌呤类似物（II，2'-F-ara-H）。通过汞法将1与6-氯嘌呤缩合，然后进行硫脲处理和产物皂化，制备6-硫嘌呤核苷（III，2'-F-ara-6MP）。III的甲基化得到6-SCH3类似物（IV）。III的阮内镍脱硫得到未取代的嘌呤核苷（V，2'-F-ara-P）。通过甲硅烷基方法将1-与2-乙酰氨基-6-氯嘌呤缩合，得到被保护的2-乙酰氨基-6-氯嘌呤核苷，其可用作鸟嘌呤和6-硫代鸟嘌呤核苷的前体（VI，2'-F-ara- G和VII，分别为2'-F-ara
• CHU, CHUNG K.;MATULIC-ADAMIC, JASENKA;HUANG, JAI-TUNG;CHOU, TING-CHAO;BUR+, CHEM. AND PHARM. BULL., 37,(1989) N, C. 336-339
  作者：CHU, CHUNG K.、MATULIC-ADAMIC, JASENKA、HUANG, JAI-TUNG、CHOU, TING-CHAO、BUR+

  DOI：——

  日期：——
• MARQUEZ, VICTOR E.;TSENG, CHRISTOPHER K. -H.;MITSUYA, HIROAKI;AOKI, SHIZU+, J. MED. CHEM., 33,(1990) N, C. 978-985
  作者：MARQUEZ, VICTOR E.、TSENG, CHRISTOPHER K. -H.、MITSUYA, HIROAKI、AOKI, SHIZU+

  DOI：——

  日期：——