(+/-)-trans-1-<2-(hydroxymethyl)cyclopentylmethyl>uracil

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (+/-)-trans-1-<2-(hydroxymethyl)cyclopentylmethyl>uracil
• 英文别名: 1-{[(1R,2R)-2-(hydroxymethyl)cyclopentyl]methyl}pyrimidine-2,4(1H,3H)-dione；1-[[(1R,2R)-2-(hydroxymethyl)cyclopentyl]methyl]pyrimidine-2,4-dione
• 化学式: C₁₁H₁₆N₂O₃
• 分子量: 224.26
• InChiKey: UFOQKVCLMJHIKA-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-1-<2-(hydroxymethyl)cyclopentylmethyl>uracil 在 碘 、 硝酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以89%的产率得到(+/-)-trans-1-[2-(hydroxymethyl)cyclopentylmethyl]-5-iodouracil
  参考文献：
  名称：

  A Novel Approach for the Virtual Screening and Rational Design of Anticancer Compounds

  摘要：

  A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7.14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c,d.

  DOI：

  10.1021/jm991172d
• 作为产物：
  描述：

  2-(Aminomethyl)cyclopentylmethanol 在 4 A molecular sieve 、 硫酸 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 3.0h， 生成 (+/-)-trans-1-<2-(hydroxymethyl)cyclopentylmethyl>uracil
  参考文献：
  名称：

  A Novel Approach for the Virtual Screening and Rational Design of Anticancer Compounds

  摘要：

  A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7.14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c,d.

  DOI：

  10.1021/jm991172d

文献信息

• A slightly shorter route to carbocyclic nucleosides. Synthesis of (±)-<i>trans</i>-1-[2-(hydroxymethyl)cyclopentylmethyl]uracil
  作者：Lourdes Santana、Marta Teijeira、Eugenio Uriarte

  DOI：10.1002/jhet.5570360146

  日期：1999.1

  (±)-trans-1-[2-(Hydroxymethyl)cyclopentylmethyl]uracil (1) was prepared in two steps and 56% yield from 2-hydroxymethylcyclopentylmethylamine (7) and 3-methoxy-2-propenoylisocyanate (6). Isocyanate 6 was prepared from methyl 3-methoxy-2-propenoate in four steps and 38% overall yield.

  分两步制备（±）-反式-1- [2-（羟甲基）环戊基甲基]尿嘧啶（1），由2-羟甲基环戊基甲胺（7）和3-甲氧基-2-丙烯酰基异氰酸酯（6）制备产率为56％。由3-甲氧基-2-丙烯酸甲酯以四个步骤制备异氰酸酯6，总产率为38％。
• A Novel Approach for the Virtual Screening and Rational Design of Anticancer Compounds
  作者：Ernesto Estrada、Eugenio Uriarte、Alina Montero、Marta Teijeira、Lourdes Santana、Erik De Clercq

  DOI：10.1021/jm991172d

  日期：2000.5.1

  A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7.14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c,d.

表征谱图