6-benzyl-1-[(benzyloxy)methyl]-5-isopropylpyrimidine-2,4(1H,3H)-dione | 175739-42-1

• 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: 6-benzyl-1-[(benzyloxy)methyl]-5-isopropylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-benzyl-1-(benzyloxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione；6-benzyl-1-benzyloxymethyl-5-isopropyluracil；TNK-651；6-Benzyl-1-benzyloxymethyl-5-isopropyl uracil；6-benzyl-1-(phenylmethoxymethyl)-5-propan-2-ylpyrimidine-2,4-dione
• CAS: 175739-42-1
• 化学式: C₂₂H₂₄N₂O₃
• 分子量: 364.444
• InChiKey: KSAAUHMSLCPIEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-benzyl-1-[(benzyloxy)methyl]-5-isopropylpyrimidine-2,4(1H,3H)-dione 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以53%的产率得到6-benzyl-1-(benzyloxymethyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase

  摘要：

  A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of human immunodeficiency virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.

  DOI：

  10.1021/ml1002162
• 作为产物：
  描述：

  4-苯基乙酰乙酸乙酯 在 N,O-双三甲硅基乙酰胺 、 四丁基溴化铵 、 sodium ethanolate 、 potassium carbonate 、 氯乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 6-benzyl-1-[(benzyloxy)methyl]-5-isopropylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Emivirine及其类似物的新型高效灵活合成途径

  摘要：

  开发了经过修订的合成路线，该路线是通过从麦芽糖酸中转化得到的适当取代的β-酮酯制得的艾米韦林（MKC-442）。该方法可用于多种MKC-442类似物的合成，并为它们进行系统的生物学评估开辟了道路。

  DOI：

  10.1002/jhet.987

文献信息

• 3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase
  作者：Jing Tang、Kasthuraiah Maddali、Mathieu Metifiot、Yuk Y. Sham、Robert Vince、Yves Pommier、Zhengqiang Wang

  DOI：10.1021/jm1014378

  日期：2011.4.14

  Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (IN Is). We have previously disclosed a novel dual inhibitor scaffold of HIV IN and reverse transcriptase (RT). Here we report the complete structure activity relationship (SAR), molecular modeling, and resistance profile of this inhibitor type on IN inhibition. These studies support an antiviral mechanism of dual inhibition against both IN and RT and validate 3-hydroxypyrimidine-2,4-diones as an IN inhibitor scaffold.
• N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase
  作者：Jing Tang、Kasthuraiah Maddali、Christine D. Dreis、Yuk Y. Sham、Robert Vince、Yves Pommier、Zhengqiang Wang

  DOI：10.1021/ml1002162

  日期：2011.1.13

  A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of human immunodeficiency virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.
• New Efficient and Flexible Synthetic Route to Emivirine and Its Analogs
  作者：Li Li、Liying Ma、Xiaowei Wang、Junyi Liu

  DOI：10.1002/jhet.987

  日期：2013.1

  A revised synthetic route to Emivirine (MKC‐442) via properly substituted β‐keto ester converted from Meldrum's Acid was developed. This method could be applied to the synthesis of a variety of MKC‐442 analogues and open the way for their systematic biological evaluation.

  开发了经过修订的合成路线，该路线是通过从麦芽糖酸中转化得到的适当取代的β-酮酯制得的艾米韦林（MKC-442）。该方法可用于多种MKC-442类似物的合成，并为它们进行系统的生物学评估开辟了道路。