6-chloro-3-methyl-1-(2-methylpropyl)-1H-pyrimidine-2,4(1H,3H)-dione | 214636-53-0

• 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-chloro-3-methyl-1-(2-methylpropyl)-1H-pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-chloro-3-methyl-1-(2'-methylpropyl)-2,4-(1H,3H)-pyrimidinedione；6-chloro-1-isobutyl-3-methylpyrimidine-2,4(1H,3H)-dione；6-chloro-3-methyl-1-(2-methylpropyl)pyrimidine-2,4[1H,3H]-dione；6-chloro-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione
• CAS: 214636-53-0
• 化学式: C₉H₁₃ClN₂O₂
• 分子量: 216.667
• InChiKey: NSZSICWLXFCCRN-UHFFFAOYSA-N

物化性质

• 沸点：
  271.6±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-3-methyl-1-(2-methylpropyl)-1H-pyrimidine-2,4(1H,3H)-dione 在 哌啶 、 肼 作用下， 反应 16.0h， 生成 2-[(6-Chloroquinolin-4-yl)methyl]-5-methyl-3-(3-methylimidazol-4-yl)-7-(2-methylpropyl)pyrazolo[3,4-d]pyrimidine-4,6-dione
  参考文献：
  名称：

  Design of inhibitors of Helicobacter pylori glutamate racemase as selective antibacterial agents: Incorporation of imidazoles onto a core pyrazolopyrimidinedione scaffold to improve bioavailabilty

  摘要：

  Structure-activity relationships are presented around a series of pyrazolopyrimidinediones that inhibit the growth of Helicobacter pylori by targeting glutamate racemase, an enzyme that provides d-glutamate for the construction of N-acetylglucosamine-N-acetylmuramic acid peptidoglycan subunits assimilated into the bacterial cell wall. Substituents on the inhibitor scaffold were varied to optimize target potency, antibacterial activity and in vivo pharmacokinetic stability. By incorporating an imidazole ring at the 7-position of scaffold, high target potency was achieved due to a hydrogen bonding network that occurs between the 3-position nitrogen atom, a bridging water molecule and the side chains Ser152 and Trp244 of the enzyme. The lipophilicity of the scaffold series proved important for expression of antibacterial activity. Clearances in vitro and in vivo were monitored to identify compounds with improved plasma stability. The basicity of the imidazole may contribute to increased aqueous solubility at lower pH allowing for improved oral bioavailability.

  DOI：

  10.1016/j.bmcl.2012.07.004
• 作为产物：
  描述：

  1-甲基巴比妥酸 在 potassium carbonate 、 三氯氧磷 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 6-chloro-3-methyl-1-(2-methylpropyl)-1H-pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  WO2007/143705

  摘要：

  公开号：

文献信息

• [EN] PTERIDINE DIONE MONOCARBOXYLATE TRANSPORTER INHIBITORS<br/>[FR] INHIBITEURS PTÉRIDINE DIONE DU TRANSPORTEUR DE MONOCARBOXYLATE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2016118823A1

  公开（公告）日：2016-07-28

  The invention provides compounds effective as inhibitors of monocarboxylate transporters such as MCT1 and MCT4, which can be used for treatment of medical conditions wherein treatment of the condition with a compound having an inhibitor effect on MCT1, MCT4, or both is medically indicated. Compounds of the invention can have antitumor, antidiabetes, anti-inflammatory, or immunosuppressive pharmacological effects, and can be effective for treatment of cancer and of type II diabetes.

  本发明提供了有效作为单羧酸转运蛋白如MCT1和MCT4抑制剂的化合物，这些化合物可用于治疗医学状况，其中使用对MCT1、MCT4或两者具有抑制作用的化合物治疗该状况在医学上是适宜的。本发明的化合物可能具有抗肿瘤、抗糖尿病、抗炎或免疫抑制的药理作用，并且可有效治疗癌症和II型糖尿病。
• Pyrazolo[3,4-d]pyrimidineone compounds
  申请人：Astra Pharmaceuticals, Ltd.

  公开号：US06028074A1

  公开（公告）日：2000-02-22

  The invention relates to pharmaceutically useful pyrazolo[3,4-d]pyrimidinedione compounds, processes for their production, pharmaceutical compositions containing them and their use for the treatment of various diseases.

  这项发明涉及到在药用上有用的吡唑并[3,4-d]嘧啶二酮化合物，其生产过程，含有它们的药物组合物以及它们用于治疗各种疾病的用途。
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：INTRA CELLULAR THERAPIES INC

  公开号：WO2009073210A1

  公开（公告）日：2009-06-11

  1- or 2- or 7-(substituted)-3-(optionally hetero)arylamino-[lH, 2H]-pyrazolo[3,4-d] pyrimidine-4,6(5H, 7H)-dione derivatives, in free, salt or prodrug form, are useful as pharmaceuticals, particularly as phosphodiesterase 1 inhibitors, useful for the treatment of diseases involving disorders of the dopamine Dl receptor intracellular pathway, such as Parkinson's disease, depression, narcolepsy and damage to cognitive function, e.g., in schizophrenia or disorders that may be ameliorated through enhanced progesterone - signaling pathway, e.g., female sexual dysfunction.

  1-或2-或7-(取代)-3-(可选杂)芳基氨基-[1H, 2H]-吡唑[3,4-d]吡嘧啶-4,6(5H, 7H)-二酮衍生物，以自由、盐或前药形式存在，可用作药物，特别是磷酸二酯酶1抑制剂，用于治疗涉及多巴胺D1受体细胞内通路紊乱的疾病，如帕金森病、抑郁症、嗜睡症和损害认知功能，例如精神分裂症或可以通过增强孕酮-信号通路改善的疾病，例如女性性功能障碍。
• Exploring the functionalisation of the thieno[2,3- d ]pyrimidinedione core: Late stage access to highly substituted 5-carboxamide-6-aryl scaffolds
  作者：Kerry M. O'Rourke、Erin S. Johnstone、Holger M. Becker、Sally L. Pimlott、Andrew Sutherland

  DOI：10.1016/j.tet.2018.06.019

  日期：2018.7

  functionalisation of this core motif via bromination of the thiophene ring and a subsequent Suzuki-Miyaura reaction as the key steps permitted access to a novel library of 5-carboxamide-6-aryl analogues. The physicochemical properties of these compounds were determined, generating an insight into the potential bioavailability of these scaffolds. Based on these results, a selection of the novel 5-carboxamide-6-aryl

  噻吩并[2,3- d ]嘧啶二酮核心被发现是一系列药物活性化合物的组成部分，但是，这些支架的合成方法依赖于获得官能化的，高度取代的噻吩的途径。在这里，我们描述了一种制备5-羧酰胺-6-芳基类似物的新方法，该方法涉及从容易获得的巯基尿嘧啶衍生物两步合成噻吩并[2,3- d ]嘧啶二酮核心。用3-溴丙酮酸乙酯进行硫代烷基化，然后由多磷酸介导的环化和脱水使噻吩并[2,3- d]嘧啶二酮单元。该核心基序的后期功能化是通过噻吩环的溴化和随后的Suzuki-Miyaura反应作为关键步骤，从而可以访问5-羧酰胺-6-芳基类似物的新文库。确定了这些化合物的理化性质，从而深入了解了这些支架的潜在生物利用度。基于这些结果，测试了新的5-羧酰胺-6-芳基类似物的选择作为非洲爪蟾卵母细胞中单羧酸盐转运蛋白1、2和4的乳酸摄取抑制剂。
• Thieno&lsqb;2,3-d&rsqb;pyrimidine-2,4-diones
  申请人：AstraZeneca AB

  公开号：US06300334B1

  公开（公告）日：2001-10-09

  Compounds of formula (I): wherein R1, R2, and R3 are defined in the specification. The compounds are useful for treating or reducing the risk of reversible obstructive airways disease.

  式(I)的化合物：其中R1、R2和R3在说明书中有定义。这些化合物可用于治疗或减少可逆性阻塞性呼吸道疾病的风险。