ZSM-I-287S

• 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: ZSM-I-287S
• 英文别名: (E)-2,6-diamino-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene]-methyl}purine；(E)-2,6-Diamino-9-{[2,2-bis(hydroxymethyl)cyclopropylidene]methyl}purine；[(2E)-2-[(2,6-diaminopurin-9-yl)methylidene]-1-(hydroxymethyl)cyclopropyl]methanol
• 化学式: C₁₁H₁₄N₆O₂
• 分子量: 262.271
• InChiKey: YZDFBHZWTFMZPF-QHHAFSJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  diethyl bromoisopropylidenemalonate 在 氨 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.5h， 生成 ZSM-I-287S
  参考文献：
  名称：

  Synthesis and Antiviral Activity of (Z)- and (E)-2,2-[Bis(hydroxymethyl)cyclopropylidene]methylpurines and -pyrimidines:  Second-Generation Methylenecyclopropane Analogues of Nucleosides

  摘要：

  The second generation of methylenecyclopropane analogues of nucleosides 5a-5i and 6a-6i was synthesized and evaluated for antiviral activity. The 2,2-bis(hydroxymethyl)methylenecyclopropane (11) was converted to dibromo derivative 7 via acetate 12. Alkylation-elimination of adenine (16) with 7 afforded the Z/E mixture of acetates 17 + 18, which was deacetylated to give analogues 5a and 6a separated by chromatography. A similar reaction with 2-amino-6-chloropurine (19) afforded acetates 20 + 21 and, after deprotection and separation, isomers 5f and 6f. The latter served as starting materials for synthesis of analogues 5b, 5e, 5g-5i and 6b, 6e, 6g-6i. Alkylation-elimination of N(4)-acetylcytosine (22) with 7 afforded a mixture of isomers 5c + 6c which were separated via N(4)-benzoyl derivatives 23 and 24. Deprotection furnished analogues 5c and 6c. Alkylation of 2,4-bis(trimethylsilyloxy)-5-methylpyrimidine (25) with 7 led to bromo derivative 26. Elimination of HBr followed by deacetylation and separation gave thymine analogues 5d and 6d. The guanine Z-isomer 5b was the most effective against human and murine cytomegalovirus (HCMV and MCMV) with EC(50) = 0.27-0.49 muM and no cytotoxicity. The 6-methoxy analogue 5g was also active (EC(50) = 2.0-3.5 muM) whereas adenine Z-isomer 5a was less potent (EC(50) = 3.6-11.7 muM). Cytosine analogue 5c was moderately effective, but 2-amino-6-cyclopropylamino derivative 5e was inactive. All E-isomers were devoid of anti-CMV activity, and none of the analogues was significantly active against herpes simplex viruses (HSV-1 or HSV-2). The potency against Epstein-Barr virus (EBV) was assay-dependent. In Daudi cells, the E-isomers of 2-amino-6-cyclopropylamino- and 2,6-diaminopurine derivatives 6e and 6h were the most potent (EC(50) approximate to 0.3 muM), whereas only the thymine Z-isomer 5d was active (EC(50) = 4.6 muM). Guanine Z-derivative 5b was the most effective compound in H-1 cells (EC(50) = 7 muM). In the Z-series, the 2-amino-6-methoxypurine analogue 5g was the most effective against varicella zoster virus (VZV, EC(50) = 3.3 muM) and 2,6-diaminopurine 5h against hepatitis B virus (HBV, EC(50) = 4 muM). Adenine analogues 5a and 6a were moderately active as substrates for adenosine deaminase.

  DOI：

  10.1021/jm030316s

文献信息

• 2,2-bis-(hydroxymethyl)cyclopropylidenemethyl-purines and pyrmindines as antiviral agents
  申请人：Zemlicka Jiri

  公开号：US20050113393A1

  公开（公告）日：2005-05-26

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  具有抗病毒活性的化合物具有以下公式：其中B是嘌呤或嘧啶杂环环或碱基。在一个首选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤）、6-羟基嘌呤（次黄嘌呤）、2-氨基-6-羟基嘌呤（鸟嘌呤）、2,6-二氨基嘌呤，2-氨基-6-叠氮基嘌呤，2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤，2-氨基-6-氟嘌呤，2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤，2-氨基-6-环丙基氨基嘌呤，2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基嘌呤，2-氨基-6-硫嘌呤，2-氨基-6-烷硫代嘌呤，3-脱氮嘌呤，7-脱氮嘌呤和8-氮嘌呤。嘧啶包括胞嘧啶、尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基代胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基基团的衍生物和6-氮杂嘧啶。
• 2,2-Bis-(hydroxymethyl)cyclopropylidenemethyl-Purines and -Pyrimidines As Antiviral Agents
  申请人：Zemlicka Jiri

  公开号：US20090118308A1

  公开（公告）日：2009-05-07

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  对病毒具有活性的化合物具有以下公式：其中B是嘌呤或嘧啶杂环环或碱基。在优选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤），6-羟基嘌呤（次黄嘌呤），2-氨基-6-羟基嘌呤（鸟嘌呤），2,6-二氨基嘌呤，2-氨基-6-叠氮基嘌呤，2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤，2-氨基-6-氟嘌呤，2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤，2-氨基-6-环丙基氨基嘌呤，2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基取代的嘌呤，2-氨基-6-硫代嘌呤，2-氨基-6-烷基硫代取代嘌呤，3-去氮嘌呤，7-去氮嘌呤和8-氮杂嘧啶。嘧啶包括胞嘧啶，尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基取代的胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基的衍生物和6-氮杂嘧啶。
• 2,2-BIS-(HYDROXYMETHYL)CYCLOPROPYLIDENEMETHYL-PURINES AND -PYRIMIDINES AS ANTIVIRAL AGENTS
  申请人：Zemlicka Jiri

  公开号：US20110275652A1

  公开（公告）日：2011-11-10

  Compounds which are active against viruses have the following formulas: wherein B is a purine or pyrimidine heterocyclic ring or base. In a preferred embodiment, the purine include 6-aminopurine (adenine), 6-hydroxypurine (hypoxanthine), 2-amino-6-hydroxypurine (guanine), 2,6-diamino-purine, 2-amino-6-azidopurine, 2-amino-6-halo substituted purines such as 2-amino-6-chloropurine, 2-amino-6-fluoropurine, 2-amino-6-alkoxypurines such as 2-amino-6-methoxypurine, 2-amino-6-cyclopropylaminopurine, 2-amino-6-alkylamino or 2-amino-6-dialkylamino substituted purines, 2-amino-6-thiopurine, 2-amino-6-alkylthio substituted purines, 3-deazapurines, 7-deazapurines and 8-azapurines. The pyrimidine incorporates cytosine, uracil and thymine, 5-halo substituted cytosines and uracils, 5-alkyl substituted cytosines and uracils including derivatives with a saturated or unsaturated alkyl group and 6-azapyrimidines.

  具有抗病毒活性的化合物具有以下公式：其中B是一种嘌呤或嘧啶杂环环或碱基。在优选实施例中，嘌呤包括6-氨基嘌呤（腺嘌呤）、6-羟基嘌呤（次黄嘌呤）、2-氨基-6-羟基嘌呤（鸟嘌呤）、2,6-二氨基嘌呤、2-氨基-6-叠氮基嘌呤、2-氨基-6-卤代嘌呤，例如2-氨基-6-氯嘌呤、2-氨基-6-氟嘌呤、2-氨基-6-烷氧基嘌呤，例如2-氨基-6-甲氧基嘌呤、2-氨基-6-环丙胺基嘌呤、2-氨基-6-烷基氨基或2-氨基-6-二烷基氨基取代的嘌呤，2-氨基-6-硫代嘌呤，2-氨基-6-烷基硫代取代的嘌呤，3-脱氮嘌呤，7-脱氮嘌呤和8-氮杂嘧啶。嘧啶包括胞嘧啶、尿嘧啶和胸腺嘧啶，5-卤代胞嘧啶和尿嘧啶，5-烷基取代的胞嘧啶和尿嘧啶，包括具有饱和或不饱和烷基的衍生物和6-氮杂嘧啶。
• 2,2-BIS(HYDROXYMETHYL)CYCLOPROPYLIDENEMETHYL - PURINES AND -PYRIMIDINES AS ANTIVIRAL AGENTS
  申请人：WAYNE STATE UNIVERSITY

  公开号：EP1490368B1

  公开（公告）日：2011-08-03
• US7393855B2
  申请人：——

  公开号：US7393855B2

  公开（公告）日：2008-07-01