2-(1-羟基乙基)嘧啶-4(3H)-酮 | 299397-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-(1-羟基乙基)嘧啶-4(3H)-酮
• 英文名称: (R,S)-2-(1-hydroxyethyl)-4-hydroxy pyrimidine
• 英文别名: 2-(1-hydroxyethyl)pyrimidin-4-ol；2-(1-hydroxyethyl)-3H-pyrimidin-4-one；2-(1-hydroxyethyl)pyrimidin-4(3H)-one；2-(1-hydroxyethyl)-1H-pyrimidin-6-one
• CAS: 299397-03-8
• 化学式: C₆H₈N₂O₂
• 分子量: 140.142
• InChiKey: PSUSZVMSXODUAH-UHFFFAOYSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-羟基乙基)嘧啶-4(3H)-酮 在 Lipase P₃₀ 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 (R)-1-(4-methanesulfonyloxy-pyrimidin-2-yl)-ethyl butyrate
  参考文献：
  名称：

  Sorbitol Dehydrogenase Inhibitors (SDIs):  A New Potent, Enantiomeric SDI, 4-[2-1R-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide

  摘要：

  We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10x more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.

  DOI：

  10.1021/jm0102001
• 作为产物：
  描述：

  2-羟基丙脒 、 sodium 3-ethoxy-3-oxoprop-1-en-1-olate 在 水 作用下， 生成 2-(1-羟基乙基)嘧啶-4(3H)-酮
  参考文献：
  名称：

  Sorbitol Dehydrogenase Inhibitors (SDIs):  A New Potent, Enantiomeric SDI, 4-[2-1R-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide

  摘要：

  We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10x more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.

  DOI：

  10.1021/jm0102001

文献信息

• Compounds for treating and preventing diabetic complications
  申请人：Pfizer Inc.

  公开号：US06294538B1

  公开（公告）日：2001-09-25

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R is as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an NHE-1 inhibitor and to methods of treating cardiomyopathy and other heart-related problems therewith. This invention is also directed to certain intermediates used in the synthesis of the compounds of formula I and to processes for preparing those intermediates.

  这项发明涉及式I的山梨醇脱氢酶抑制化合物，其中R如规范中所定义。这项发明还涉及含有这些化合物的药物组合物，以及通过向患有糖尿病且因此有发生这些并发症风险的哺乳动物施用这些化合物来治疗或预防糖尿病并发症，特别是糖尿病神经病变、糖尿病肾病和糖尿病心肌病。这项发明还涉及含有本发明式I化合物与醛糖还原酶抑制剂的组合物的药物组合物，以及用于治疗或预防糖尿病并发症的方法。这项发明还涉及含有本发明式I化合物与NHE-1抑制剂的组合物的药物组合物，以及用于治疗心肌病和其他心脏相关问题的方法。这项发明还涉及用于合成式I化合物的某些中间体以及制备这些中间体的方法。
• [EN] 2- (PIPERIDIN-1-YL) -4-HETEROCYCLYL-THIAZOLE-5-CARBOXYLIC ACID DERIVATIVES AGAINST BACTERIAL INFECTIONS<br/>[FR] DÉRIVÉS DE L'ACIDE 2-(PIPÉRIDINE-1-YL)-4-HÉTÉROCYCLYL-THIAZOLE-5-CARBOXYLIQUE UTILISÉS POUR LUTTER CONTRE LES INFECTIONS BACTÉRIENNES
  申请人：ASTRAZENECA AB

  公开号：WO2010067123A1

  公开（公告）日：2010-06-17

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described. Ring A is selected from formula (a), (b) or (b'):

  化合物的结构式（I）及其药用盐已经描述。还描述了它们的制备方法、含有它们的药物组合物、它们作为药物的用途以及它们在治疗细菌感染中的用途。环A从式（a）、（b）或（b'）中选择。
• Sorbitol dehydrogenase inhibitors
  申请人：Pfizer Inc.

  公开号：US06414149B1

  公开（公告）日：2002-07-02

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an NHE-1 inhibitor and to methods of treating cardiomyopathy and other heart-related problems therewith. This invention is also directed to certain intermediates used in the synthesis of the compounds of formula I and to processes for preparing those intermediates.

  本发明涉及式I的山梨醇脱氢酶抑制化合物，其中R1、R2和R3如规范中定义。本发明还涉及含有这些化合物的药物组合物，以及通过向患有糖尿病且因此有发展这些并发症风险的哺乳动物投与这些化合物来治疗或预防糖尿病并发症，特别是糖尿病神经病变、糖尿病肾病、糖尿病微血管病、糖尿病大血管病和糖尿病心肌病。本发明还涉及一种含有本发明式I化合物与醛糖还原酶抑制剂的组合物的药物组合物，以及用于治疗或预防糖尿病并发症的方法。本发明还涉及一种含有本发明式I化合物与NHE-1抑制剂的组合物的药物组合物，以及用于治疗心肌病和其他相关心脏问题的方法。本发明还涉及合成式I化合物的某些中间体以及制备这些中间体的方法。
• SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711
  作者：Margaret Y. Chu-Moyer、William E. Ballinger、David A. Beebe、James B. Coutcher、Wesley W. Day、Jiancheng Li、Peter J. Oates、R.Matthew Weekly

  DOI：10.1016/s0960-894x(02)00208-1

  日期：2002.6

  711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechanism for the in vivo epimerization is proposed involving an oxidation-reduction pathway of the secondary benzylic alcohol, in contrast to an acid/base-promoted epimerization of the same center during

  对CP-470,711立体异构体的SAR研究表明，大鼠体内发生了差向异构。进一步的代谢研究表明，在狗中没有发生差向异构化，并且在人类中没有期望的差向异构化。与化学合成过程中相同中心的酸/碱促进的差向异构化相反，提出了一种体内差向异构化的机制，涉及仲苄醇的氧化-还原途径。
• [EN] AMINOPYRIMIDINES AS SORBITOL DEHYDROGENASE INHIBITORS<br/>[FR] AMINOPYRIMIDINES COMME INHIBITEURS DE SORBITOL DESHYDROGENASE
  申请人：PFIZER PROD INC

  公开号：WO2000059510A1

  公开（公告）日：2000-10-12

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of formula (I), wherein R?1, R2 and R3¿ are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefor at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula (I) of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula (I) of this invention with an NHE-1 inhibitor and to methods of treating cardiomyopathy and other heart-related problems therewith. This invention is also directed to certain intermediates used in the synthesis of the compounds of formula (I) and to processes for preparing those intermediates.

  本发明涉及式（I）的山梨醇脱氢酶抑制剂，其中R1、R2和R3在说明书中定义。本发明还涉及含有这些化合物的药物组合物，以及通过将这些化合物用于患有糖尿病并因此有患上这些并发症风险的哺乳动物进行治疗或预防糖尿病并发症，特别是糖尿病神经病变、糖尿病肾病、糖尿病微血管病、糖尿病大血管病和糖尿病心肌病的方法。本发明还涉及一种包含本发明式（I）化合物和醛还原酶抑制剂的药物组合物以及用于治疗或预防糖尿病并发症的方法。本发明还涉及一种包含本发明式（I）化合物和NHE-1抑制剂的药物组合物以及用于治疗心肌病和其他心脏相关问题的方法。本发明还涉及用于合成式（I）化合物的某些中间体以及制备这些中间体的方法。