3-deoxy-3-(hydroxymethyl)-1,2-O-(1-methylethylidene)-5-O-(phenylmethyl)-α-D-ribofuranose | 34311-67-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-deoxy-3-(hydroxymethyl)-1,2-O-(1-methylethylidene)-5-O-(phenylmethyl)-α-D-ribofuranose
• 英文别名: 5-O-benzyl-3-deoxy-3-(hydroxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose；3-Deoxy-3-(hydroxymethyl)-1,2-O-(1-methyl-ethylidene)-5-O-(PhenYlmethYl)-α-D-ribo-furanose；[(3aR,5S,6R,6aR)-2,2-dimethyl-5-(phenylmethoxymethyl)-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]methanol
• CAS: 34311-67-6
• 化学式: C₁₆H₂₂O₅
• 分子量: 294.348
• InChiKey: YMUBJSGFXORHNV-KBUPBQIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-deoxy-3-(hydroxymethyl)-1,2-O-(1-methylethylidene)-5-O-(phenylmethyl)-α-D-ribofuranose 在 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 9.5h， 生成 5-O-benzyl-3-deoxy-3-[(p-anisyloxy)methyl]-D-ribofuranose
  参考文献：
  名称：

  3'-C支链取代的核苷和核苷酸作为结核分枝杆菌胸苷单磷酸激酶的有效抑制剂。

  摘要：

  结核分枝杆菌（TMPKmt）的胸苷单磷酸激酶（TMPK）代表了一种阻断细菌DNA合成的有吸引力的靶标。为了找到TMPKmt的高亲和力抑制剂，通过在胸苷单磷酸（dTMP）支架的3'-位置引入各种取代基来探索酶在3'-位置的空腔。从一个关键的中间体（23）合成了2'-脱氧核糖（3-6）和核糖系列（7，8）中的各种3'-C支链取代的核苷酸。2'-脱氧类似物被证明是TMPKmt的有效抑制剂：3'-CH（2）NH（2）（4），3'-CH（2）N（3）（3）和3'-CH（2 F（5）个核苷酸在该系列中表现出最高亲和力，K（i）值分别为10.5、12和15 microM。这些结果表明，TMPKmt可耐受在3'-位引入空间上要求的取代基。核糖类似物经历了显着的亲和力降低，这可能是由于Tyr103在2'位置附近的空间位阻。尽管5'-O-磷酸化的化合物对酶具有更高的亲和力，但亲本核苷通常以相同的数量级显示出对

  DOI：

  10.1021/jm021108n
• 作为产物：
  描述：

  5-O-benzyl-3-oxo-1,2-O-isopropylidene-α-D-xylofuranose 在 sodium hydroxide 、 硼烷四氢呋喃络合物 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 5.08h， 生成 3-deoxy-3-(hydroxymethyl)-1,2-O-(1-methylethylidene)-5-O-(phenylmethyl)-α-D-ribofuranose
  参考文献：
  名称：

  Synthesis and antiviral activity of novel isonucleoside analogs

  摘要：

  A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3alpha,4beta,5alpha)]-2-amino-1,9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereospecifically achieved starting from 1,2-isopropylidene-D-xylofuranose (10). An efficient two-step reduction of the anomeric center of bis-acetate 18 involved formation of the chloride intermediate 19, followed by diisobutylaluminum hydride reduction. Tosylation of the resulting alcohol 20 provided the key intermediate 21, which was coupled with a variety of nucleobase anions. Several members of this new class of compounds possess activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). Compound 7 exhibits potent and selective activity against thymidine kinase encoding herpesviruses, in particular, HSV-1 and HSV-2. Evaluation of compound 7 for inhibition of WI-38 cell growth indicated an ID50 of > 700 muM. Although the antiherpetic activity in vitro of 7 is less than that of acyclovir (1), compound 7 displays superior efficacy in mouse model infections. The (bromovinyl)uridine analog 8 (BMS-181,165) also exhibits selective activity against HSV-1 and VZV, with no cytostatic effect on WI-38 cell growth at > 800 muM. Compound 8 is active against simian varicella virus and is efficacious in the corresponding monkey model.

  DOI：

  10.1021/jm00061a013

文献信息

• Purinyl tetrahydrofurans
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05059690A1

  公开（公告）日：1991-10-22

  Antiviral activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1 is a purine or pyrimidine base or an analog thereof and R.sub.2 and R.sub.3 are independently hydrogen, --PO.sub.3 H.sub.2 or ##STR2## wherein X.sub.7 is hydrogen, alkyl, substituted alkyl or aryl.

  化合物具有以下结构式的抗病毒活性：##STR1##及其药学上可接受的盐，其中R.sub.1是嘌呤或嘧啶碱基或其类似物，R.sub.2和R.sub.3分别是氢、--PO.sub.3 H.sub.2或##STR2##其中X.sub.7是氢、烷基、取代烷基或芳基。
• Purinyl and pyrimidinyl tetrahydrofurans
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0394893A2

  公开（公告）日：1990-10-31

  Antiviral activity is exhibited by compounds having the formula and pharmaceutically acceptable salts thereof wherein R1 is a purine or pyrimidine base or an analog thereof and R2 and R3 are independently hydrogen, -PO3H2 or - -X7, wherein X7 is hydrogen, alkyl, substituted alkyl or aryl.

  具有以下式子的化合物具有抗病毒活性 及其药学上可接受的盐类，其中 R1 是嘌呤或嘧啶碱或其类似物，R2 和 R3 独立地是氢、-PO3H2 或 -X7，其中 X7 是氢、烷基、取代的烷基或芳基。
• Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides
  作者：Tai Shun Lin、Ju Liang Zhu、Ginger E. Dutschman、Yung Chi Cheng、William H. Prusoff

  DOI：10.1021/jm00055a006

  日期：1993.2

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.
• US5059690A
  申请人：——

  公开号：US5059690A

  公开（公告）日：1991-10-22
• US5164520A
  申请人：——

  公开号：US5164520A

  公开（公告）日：1992-11-17