3-deoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose | 1026404-30-7

• 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-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose
• 英文别名: (3R,4S,5S)-4,5-bis(phenylmethoxymethyl)oxolane-2,3-diol
• CAS: 1026404-30-7
• 化学式: C₂₀H₂₄O₅
• 分子量: 344.408
• InChiKey: JBXOSPCKVDKISN-SDWZKWEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  68.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 3-deoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose 在 吡啶 作用下， 反应 7.5h， 生成 1,2-O-diacetyl-5-O-benzyl-3-<(benzyloxy)methyl>-3-deoxy-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
• 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 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 11.92h， 生成 3-deoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-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

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

  公开号：US05145960A1

  公开（公告）日：1992-09-08

  Antiviral activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1 is a 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.

  具有以下式子的化合物及其药学上可接受的盐表现出抗病毒活性：##STR1##其中R.sub.1是嘧啶碱基或其类似物，R.sub.2和R.sub.3独立地是氢、--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