benzyl 2-[2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]acetate | 176907-02-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl 2-[2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]acetate
• 英文别名: benzyl (2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetate；1-benzyloxycarbonylmethyl-2,4-dioxopyrimidine；benzyl 2-(2,4-dioxopyrimidin-1-yl)acetate
• CAS: 176907-02-1
• 化学式: C₁₃H₁₂N₂O₄
• 分子量: 260.249
• InChiKey: GHQBNJDEIFXXST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 2-[2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]acetate 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 12.25h， 生成 tert-butyl 2-(3-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethyl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)acetate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x
• 作为产物：
  描述：

  苯甲醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 benzyl 2-[2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]acetate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x

文献信息

• Design, Synthesis, and Evaluation of a Biomimetic Artificial Photolyase Model
  作者：Olaf Wiest、Christopher B. Harrison、Nicolas J. Saettel、Radek Cibulka、Mirjam Sax、Burkhard König

  DOI：10.1021/jo0494329

  日期：2004.11.1

  photolyase models that recognize pyrimidine dimers in protic and aprotic organic solvents as well as in water through a combination of charge and hydrogen-bonding interactions and use a mimic of the flavine to achieve repair through reductive photoinduced electron transfer are presented. Fluorescence and NMR titration studies show that it forms a 1:1 complex with pyrimidine dimers with binding constants

  提出了两种新的人工光解酶模型，它们通过结合电荷和氢键相互作用识别质子和非质子有机溶剂以及水中的嘧啶二聚体，并利用黄酮的模拟物通过还原性光诱导的电子转移实现修复。荧光和NMR滴定研究表明，它与嘧啶二聚体形成1：1的络合物，结合常数约为10 3 M - 1在乙腈或甲醇中时，在pH 7.2的水中的结合常数略低。用可见光激发该络合物通过光诱导的电子转移催化导致嘧啶二聚体的清洁和快速环还原。在水中的反应明显快于在有机溶剂中的反应。由于产物抑制，反应在较高转化率下减慢。
• Pyrrolidine derivatives and their use as chymase inhibitor
  申请人：——

  公开号：US20040102384A1

  公开（公告）日：2004-05-27

  Novel pyrrolidine derivatives, being useful as chymase inhibitor or intermediate for synthesis of the active compounds, which has the formula (I): wherein R 1 is cycloalkyl, substituted or unsubstituted phenyl or naphthyl, indanyl, thienyl, furyl, substituted or unsubstituted indolyl, benzofuryl, substituted or unsubstituted benzothienyl, etc.; R 2 is H, alkyl, phenyl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; R 3 is (i) substituted or unsubstituted monocyclic heterocyclic group, (ii) substituted or unsubstituted, benzene- or pyridine-fused heterocyclic group, or (iii) a group (a): R 4 and R 5 are independently H or OH, but R 4 and R 5 are not simultaneously H, or both form oxo; n is 0, 1, 2 or 3; or a salt thereof. 1

  新型吡咯烷衍生物，可用作针对钳酶的抑制剂或合成活性化合物的中间体，其化学式为（I）：其中R1为环烷基，取代或未取代的苯基或萘基，吲哚基，噻吩基，呋喃基，取代或未取代的吲哚基，苯并呋喃基，取代或未取代的苯并噻吩基等；R2为H，烷基，苯基-低碳基，环烷基或环烷基-低碳基；R3为（i）取代或未取代的单环杂环基，（ii）取代或未取代的苯并或吡啶融合的杂环基，或（iii）一组（a）：R4和R5独立地为H或OH，但R4和R5不同时为H，或两者形成氧化物；n为0、1、2或3；或其盐。
• Heterocyclic compounds, intermediates thereof and elastase inhibitors
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US06835714B1

  公开（公告）日：2004-12-28

  The present invention relates to a heterocyclic compound of the following formula (I-a), its ester, or a salt thereof, and a human neutrophilic elastase inhibitor containing the same as the active ingredient, etc. wherein A and B are the same or different and each is a lower alkylene group being optionally substituted by an oxo group, D is a heteromonocyclic or heterobicyclic group being optionally substituted by an oxo group, R1 and R2 are the same or different and each is a lower alkyl group, R3 and R4 are different from each other, and each is a hydrogen atom or a hydroxy group, or both combine together to form an oxo group, and R5 is 2-benzoxazolyl, trifluoromethyl, benzylamino-carbonyl, etc.

  本发明涉及以下式（I-a）的杂环化合物，其酯或其盐，以及含有其作为活性成分的人类嗜中性粒细胞弹性蛋白酶抑制剂等。其中，A和B相同或不同，每个都是可选地被氧代团取代的较低烷基烷基，D是可选地被氧代团取代的杂单环或杂双环基团，R1和R2相同或不同，每个都是较低烷基烷基，R3和R4不同，并且每个都是氢原子或羟基，或两者结合形成氧代团，R5是2-苯并噁唑基，三氟甲基，苯甲氨基羰基等。
• Synthesis and structure of (carboxymethyl)-functionalized cyclobuta-fused uracil dimers
  作者：Thomas Carell、Robert Epple、Volker Gramlich

  DOI：10.1002/hlca.19970800718

  日期：1997.11.3

  Herein, we report a convenient method for the preparation of four benzyl-ester-protected, (carboxymethyl)-functionalized cyclobuta-fused uracil dimers 1–4, including the desired cis-cisoid-cis,syn- configured isomer 1, a compound which is suitable for the preparation of catalytic antibodies, synthetic receptors, and model compounds, required for the investigation of the DNA-lesion, recognition step

  在这里，我们报道了一种方便的方法，用于制备四个苄基酯保护的，（羧甲基）官能化的环丁缩合的尿嘧啶二聚体1-4，包括所需的顺式-顺式-顺式，顺式-异构体1，适用于制备催化性抗体，合成受体和模型化合物，这是研究DNA损伤，识别步骤和DNA修复机制所必需的。各异构体的全面结构测定通过1 H-NMR，并在的情况下，顺式cisoid -顺，顺和顺式traftsoid -顺，顺二聚体通过X射线晶体结构分析，本发明还提供。
• Pyrimidine Derivatives of N-Acetylguanidine: Novel Inhibitors of Sodium-Hydrogen Exchanger 1
  作者：Alexander Ozerov、Mikhail Novikov、Alexander Spasov、Igor Iezhitsa、Natalia Gurova、Valeria Gurova

  DOI：10.3987/com-18-13904

  日期：——

  Sodium-hydrogen exchanger (Na+/H+) type 1 (NHE-1) inhibitors have been shown to protect the heart during ischaemia and early reperfusion. As such, NHE-1 inhibitors are of special interest for clinical development for the attenuation of both acute and chronic post-myocardial infarction responses. New pyrimidine derivatives of N-acetylguanidine containing fragments of uracil, thymine, and their 3-benzyl derivatives were synthesised. These compounds showed in vitro inhibitory effects on NHE-1 that were significantly higher than those of zoniporide in platelet swelling assays.