N'-(1-Benzyl-5-iodo-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-N,N-dimethyl-formamidine | 342644-46-6

• 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: N'-(1-Benzyl-5-iodo-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-N,N-dimethyl-formamidine
• 英文别名: N'-(1-benzyl-5-iodo-3-methyl-2,6-dioxopyrimidin-4-yl)-N,N-dimethylmethanimidamide
• CAS: 342644-46-6
• 化学式: C₁₅H₁₇IN₄O₂
• 分子量: 412.23
• InChiKey: WFSSGMMOESSYDB-LICLKQGHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  56.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-硝基苯乙烯 、 N'-(1-Benzyl-5-iodo-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-N,N-dimethyl-formamidine 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以70%的产率得到3-Benzyl-1-methyl-6-(3-nitro-phenyl)-1H-pyrido[2,3-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  Syntheses and evaluation of pyrido[2,3-d]pyrimidine-2,4-diones as PDE 4 inhibitors

  摘要：

  The syntheses and in vitro evaluation of a new series of pyrido[2,3-d]pyrimidine-2,4-diones bearing substituents at C-3 and/or C-4 positions on the pyridine ring are described. Some of these compounds, especially 51 and 6f, were found to be potent phosphodiesterase 4 (PDE 4) inhibitors exhibiting improved ratio of PDE 4 inhibitory activity:rolipram binding assay (RBA). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00681-8
• 作为产物：
  描述：

  (E)-N,N-dimethyl-N'-(3-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)formimidamide 在 N-碘代丁二酰亚胺 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N'-(1-Benzyl-5-iodo-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-N,N-dimethyl-formamidine
  参考文献：
  名称：

  Syntheses and evaluation of pyrido[2,3-d]pyrimidine-2,4-diones as PDE 4 inhibitors

  摘要：

  The syntheses and in vitro evaluation of a new series of pyrido[2,3-d]pyrimidine-2,4-diones bearing substituents at C-3 and/or C-4 positions on the pyridine ring are described. Some of these compounds, especially 51 and 6f, were found to be potent phosphodiesterase 4 (PDE 4) inhibitors exhibiting improved ratio of PDE 4 inhibitory activity:rolipram binding assay (RBA). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00681-8

文献信息

• Method of determining potential allosterically-binding matrix metalloproteinase inhibitors
  申请人：Andrianjara Charles

  公开号：US20050004126A1

  公开（公告）日：2005-01-06

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1′ channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

  提供了一种与MMP-13催化域发生变构作用的化合物，其中包括一个疏水基团、第一和第二氢键受体以及至少一个第三氢键受体和第二个疏水基团，最好是两者都有。上述特征的笛卡尔坐标在说明书中有定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr 247和Met 253结合，第一疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂较为开放。这些化合物特异性地抑制了基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。
• EP1361873A4
  申请人：——

  公开号：EP1361873A4

  公开（公告）日：2005-10-26
• MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1361873A2

  公开（公告）日：2003-11-19
• QUINAZOLINES AS MMP-13 INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1368324A1

  公开（公告）日：2003-12-10
• [EN] MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] INHIBITEURS DE METALLOPROTEINASE MATRICIELLE
  申请人：WARNER LAMBERT CO

  公开号：WO2002064080A2

  公开（公告）日：2002-08-22

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr247 and Met 253, the first hydrophobic group locates within the S1' channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.