2,6-dioxo-N-((1s,4s)-4-phenylcyclohexyl)-1,2,3,6-tetrahydropyrimidine-4-carboxamide

• 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: 2,6-dioxo-N-((1s,4s)-4-phenylcyclohexyl)-1,2,3,6-tetrahydropyrimidine-4-carboxamide
• 化学式: C₁₇H₁₉N₃O₃
• 分子量: 313.356
• InChiKey: WPMUNLIAPKSHRJ-BETUJISGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.52
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  94.82
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2,6-dioxo-N-((1s,4s)-4-phenylcyclohexyl)-1,2,3,6-tetrahydropyrimidine-4-carboxamide 在 溴 、 溶剂黄146 作用下， 生成 5-(cyclopentylamino)-2,6-dioxo-N-(cis-4-phenylcyclohexyl)-1,2,3,6-tetrahydropyrimidine-4-carboxamide
  参考文献：
  名称：

  Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors

  摘要：

  Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetra- hydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.

  DOI：

  10.1016/j.bmcl.2018.10.022
• 作为产物：
  描述：

  乳清酸 、 4-phenylcyclohexylamine hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以75%的产率得到2,6-dioxo-N-((1s,4s)-4-phenylcyclohexyl)-1,2,3,6-tetrahydropyrimidine-4-carboxamide
  参考文献：
  名称：

  [EN] PYRIMIDINEDIONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE
  [FR] INHIBITEURS À BASE DE PYRIMIDINEDIONECARBOXAMIDE DE LIPASE ENDOTHÉLIALE

  摘要：

  本发明提供了如规范中定义的Formula (I)的化合物，以及包含任何此类新化合物的组合物。这些化合物是内皮脂酶抑制剂，可用作药物。

  公开号：

  WO2013151877A1

文献信息

• PYRIMIDINONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150065505A1

  公开（公告）日：2015-03-05

  The present invention provides compounds of Formula (I), as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

  本发明提供了公式（I）所定义的化合物，以及包含任何此类新型化合物的组合物。这些化合物是内皮细胞脂肪酶抑制剂，可用作药物。
• PYRIMIDINEDIONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE
  申请人：Bristol-Myers Squibb Company

  公开号：EP2844643B1

  公开（公告）日：2016-11-30
• US9199946B2
  申请人：——

  公开号：US9199946B2

  公开（公告）日：2015-12-01
• [EN] PYRIMIDINEDIONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE<br/>[FR] INHIBITEURS À BASE DE PYRIMIDINEDIONECARBOXAMIDE DE LIPASE ENDOTHÉLIALE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013151877A1

  公开（公告）日：2013-10-10

  The present invention provides compounds of Formula (I), as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

  本发明提供了如规范中定义的Formula (I)的化合物，以及包含任何此类新化合物的组合物。这些化合物是内皮脂酶抑制剂，可用作药物。
• Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors
  作者：Carol H. Hu、Tammy C. Wang、Jennifer X. Qiao、Lauren Haque、Alice Y.A. Chen、David S. Taylor、Xiaohong Ying、Joelle M. Onorato、Michael Galella、Hong Shen、Christine S. Huang、Nathalie Toussaint、Yi-Xin Li、Lynn Abell、Leonard P. Adam、David Gordon、Ruth R. Wexler、Heather J. Finlay

  DOI：10.1016/j.bmcl.2018.10.022

  日期：2018.12

  Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetra- hydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.