(2R,3S,4R)-3,4-bis[(4-methoxyphenyl)methoxy]-4-(2-methylpyrazolo[1,5-a]pyrimidin-6-yl)-1-trityloxy-butan-2-ol | 1442680-13-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2R,3S,4R)-3,4-bis[(4-methoxyphenyl)methoxy]-4-(2-methylpyrazolo[1,5-a]pyrimidin-6-yl)-1-trityloxy-butan-2-ol
• 英文别名: (2R,3S,4R)-3,4-bis[(4-methoxyphenyl)methoxy]-4-(2-methylpyrazolo[1,5-a]pyrimidin-6-yl)-1-trityloxybutan-2-ol
• CAS: 1442680-13-8
• 化学式: C₄₆H₄₅N₃O₆
• 分子量: 735.88
• InChiKey: KBIWTJHWLCYIFS-DIMVBODBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  55
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  96.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R)-3,4-bis[(4-methoxyphenyl)methoxy]-4-(2-methylpyrazolo[1,5-a]pyrimidin-6-yl)-1-trityloxy-butan-2-ol 在 sodium azide 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  Discovery of Carbohybrid-Based 2-Aminopyrimidine Analogues As a New Class of Rapid-Acting Antimalarial Agents Using Image-Based Cytological Profiling Assay

  摘要：

  New antimalarial agents that exhibit multistage activities against drug-resistant strains of malaria parasites represent good starting points for developing next-generation antimalarial therapies. To facilitate the progression of such agents into the development phase, we developed an image-based parasitological screening method for defining drug effects on different asexual life cycle stages of Plasmodium falciparum. High-throughput screening of a newly assembled diversity-oriented synthetic library using this approach led to the identification of carbohybrid-based 2-aminopyrimidine compounds with fast-acting growth inhibitory activities against three laboratory strains of multidrug-resistant P. falciparum. Our structure-activity relationship study led to the identification of two derivatives (8aA and 11aA) as the most promising antimalarial candidates (mean EC50 of 0.130 and 0.096 mu M against all three P. falciparum strains, selectivity indices >600, microsomal stabilities >80%, and mouse malaria ED50 values of 0.32 and 0.12 mg/kg/day, respectively), targeting all major blood stages of multidrug-resistant P. falciparum parasites

  DOI：

  10.1021/jm5009693
• 作为产物：
  描述：

  6-O-trityl-D-glucal 在 sodium hydride 、 potassium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S,4R)-3,4-bis[(4-methoxyphenyl)methoxy]-4-(2-methylpyrazolo[1,5-a]pyrimidin-6-yl)-1-trityloxy-butan-2-ol
  参考文献：
  名称：

  Discovery of Carbohybrid-Based 2-Aminopyrimidine Analogues As a New Class of Rapid-Acting Antimalarial Agents Using Image-Based Cytological Profiling Assay

  摘要：

  New antimalarial agents that exhibit multistage activities against drug-resistant strains of malaria parasites represent good starting points for developing next-generation antimalarial therapies. To facilitate the progression of such agents into the development phase, we developed an image-based parasitological screening method for defining drug effects on different asexual life cycle stages of Plasmodium falciparum. High-throughput screening of a newly assembled diversity-oriented synthetic library using this approach led to the identification of carbohybrid-based 2-aminopyrimidine compounds with fast-acting growth inhibitory activities against three laboratory strains of multidrug-resistant P. falciparum. Our structure-activity relationship study led to the identification of two derivatives (8aA and 11aA) as the most promising antimalarial candidates (mean EC50 of 0.130 and 0.096 mu M against all three P. falciparum strains, selectivity indices >600, microsomal stabilities >80%, and mouse malaria ED50 values of 0.32 and 0.12 mg/kg/day, respectively), targeting all major blood stages of multidrug-resistant P. falciparum parasites

  DOI：

  10.1021/jm5009693

文献信息

• Synthesis of Molecular Frameworks Containing Two Distinct Heterocycles Connected in a Single Molecule with Enhanced Three-Dimensional Shape Diversity
  作者：Donghyun Lim、Seung Bum Park

  DOI：10.1002/chem.201204293

  日期：2013.5.27

  report the synthesis of fused‐triazole scaffolds that are connected by pyrimidines, pyrazoles, or pyrazolopyrimidines through carbohydrate‐derived stereodivergent linkers. Pyrimidine‐, pyrazole‐, or pyrazolopyrimidine‐based carbohybrids were constructed through condensations of the key intermediates, 2‐C‐formyl glycals, with various dinucleophiles. Fused‐triazole scaffolds were obtained through intramolecular

  在本文中，我们报道了通过糖衍生的立体发散性连接子通过嘧啶，吡唑或吡唑并嘧啶连接的稠合三唑支架的合成。嘧啶，吡唑或吡唑并嘧啶的碳杂物是通过关键中间体2- C-甲酰基缩醛与各种二亲核试剂的缩合反应构建的。使用S N通过叠氮化物和炔烃官能团将羰基杂化多元醇部分选择性官能化后，通过分子内1,3-偶极环加成获得熔融三唑支架2型烷基化或Mitsunobu反应。总的来说，这种合成方法在单个分子中提供了两个截然不同的优先亚结构，这些亚结构由衍生自丰富自然手性来源（即碳水化合物）的立体发散性二醇连接基连接。接头中生成的邻位二醇经过进一步修饰，以在两个特权结构之间实现独特的连接性，从而实现了最大的三维形状多样性，我们将其称为接头多样化策略。
• 피리미딘, 피라졸 및 피라졸로피리미딘 융합된 카보하이브리드 헤테로고리 화합물 라이브러리 및 이의 제조방법
  申请人：Seoul National University R&DB Foundation 서울대학교산학협력단(120070509242) Corp. No ▼ 114371-0009224BRN ▼119-82-03684

  公开号：KR101595939B1

  公开（公告）日：2016-02-19

  본 발명은 카보하이브리드 기반의 분자 골격에 피리미딘, 피라졸 및 피라졸로피리미딘이 융합된 카보하이브리드 헤테로고리 화합물 라이브러리에 관한 것이다.

  本发明涉及基于卡波混合物分子骨架的嘧啶、吡唑和吡唑嘧啶融合的卡波混合物杂环化合物库。