2-Morpholino-4,6-dimethyl-pyrimidin | 7749-51-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-Morpholino-4,6-dimethyl-pyrimidin
• 英文别名: 4-(4,6-dimethylpyrimidin-2-yl)morpholine
• CAS: 7749-51-1
• 化学式: C₁₀H₁₅N₃O
• mdl: MFCD00501971
• 分子量: 193.249
• InChiKey: KVFPMWGCNMMRGR-UHFFFAOYSA-N

物化性质

• 熔点：
  56-57 °C
• 沸点：
  356.8±52.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Morpholino-4,6-dimethyl-pyrimidin 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 新铜试剂 、 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.0h， 生成 2-((4,6-dimethyl-2-morpholinopyrimidin-5-yl)thio)pyrimidin-4-amine
  参考文献：
  名称：

  Heat Shock Protein 70 Inhibitors. 1. 2,5′-Thiodipyrimidine and 5-(Phenylthio)pyrimidine Acrylamides as Irreversible Binders to an Allosteric Site on Heat Shock Protein 70

  摘要：

  Heat shock protein 70 (Hsp70) is an important emerging. cancer. target whose inhibition may affect multiple cancer-associated signaling pathways and, moreover, result in significant cancer cell apoptosis. Despite considerable interest from both academia and pharmaceutical companies in the discovery and development of druglike Hsp70 inhibitors, little success has been reported so far. Here we describe structure activity relationship studies in the first rationally designed Hsp70 inhibitor class that binds to a novel allosteric pocket located in the N-terminal domain of the protein. These 2,5'-thiodipyrimidine and 5-(phenylthio)-pyrimidine acrylamides take advantage of an active cysteine embedded in the allosteric pocket to act as covalent protein modifiers upon binding. The study identifies derivatives 17a and 20a, which selectively bind to Hsp70 in cancer cells. Addition of high nanomolar to low micromolar concentrations of these inhibitors to cancer cells leads to a reduction in the steady-state levels of Hsp70-sheltered oncoproteins, an effect associated with inhibition of cancer cell growth and apoptosis. In summary, the described scaffolds represent a viable starting point for the development of druglike Hsp70 inhibitors as novel anticancer therapeutics.

  DOI：

  10.1021/jm401551n
• 作为产物：
  描述：

  Morpholine-4-carboxamidine; hydrobromide 、 乙酰丙酮 在 potassium tert-butylate 作用下， 以 乙醇 为溶剂， 反应 0.08h， 以90%的产率得到2-Morpholino-4,6-dimethyl-pyrimidin
  参考文献：
  名称：

  Substituted pyrimidine derivatives

  摘要：

  本发明涉及通式I的嘧啶衍生物或其盐及其用途。

  公开号：

  US20070066612A1

文献信息

• JANUS KINASE INHIBITOR COMPOUNDS AND METHODS
  申请人：GOODACRE SIMON CHARLES

  公开号：US20100317643A1

  公开（公告）日：2010-12-16

  The invention provides compounds of Formula I, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, B, D, R 1 , R 2 , R 4 and R 5 are defined herein, a pharmaceutical composition that includes a compound of Formula I and methods of use thereof

  这项发明提供了公式I的化合物，其立体异构体或药学上可接受的盐，其中A、B、D、R1、R2、R4和R5在此处被定义，包括公式I化合物的药物组合物以及其使用方法
• [EN] 6 - ALKYNYL PYRIDINES AS SMAC MIMETICS<br/>[FR] 6-ALCYNYLE PYRIDINES UTILISÉES COMME MIMÉTIQUES DE SMAC
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013127729A1

  公开（公告）日：2013-09-06

  This invention relates to 6-alkynyl-pyridines of general formula (I) their use as SMAC mimetics, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R5 have the meanings given in the claims and in the specification.

  这项发明涉及一般式(I)的6-炔基吡啶，它们作为SMAC模拟物的用途，含有它们的药物组合物，以及它们作为治疗和/或预防由细胞过度或异常增殖引起的疾病及相关症状（如癌症）的药物的用途。基团R1到R5的含义如索赔和说明书中所述。
• 5-Alkynyl Pyridine
  申请人：REISER Ulrich

  公开号：US20130225567A1

  公开（公告）日：2013-08-29

  5-alkynyl-pyridine of general formula (I) their use as SMAC mimetics, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R 1 to R 5 have the meanings given in the claims and in the specification.

  通用式（I）的5-炔基吡啶 它们作为SMAC模拟物的用途，含有它们的药物组合物，以及它们作为治疗和/或预防由细胞过度或异常增殖引起的疾病及相关症状（如癌症）的药物的用途。 R组 1 至R组 5 的含义如索赔和说明书中所述。
• [EN] THIAZOLOPYRIDINE COMPOUNDS, COMPOSITIONS AND THEIR USE AS TYK2 KINASE INHIBITORS<br/>[FR] COMPOSÉS DE THIAZOLOPYRIDINE, COMPOSITIONS ET LEUR UTILISATION COMME INHIBITEURS DE LA KINASE TYK2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015091584A1

  公开（公告）日：2015-06-25

  Provided are thiazolopyridine compounds that are inhibitors of TYK2 kinase, compositions containing these compounds and methods for treating diseases mediated by TYK2 kinase. In particular, provided are compounds of Formula (I), (II) or (III), stereoisomers, tautomers, solvates, prodrugs or pharmaceutically acceptable salts thereof, where X, R0, R1, R2, R3, R4 and R5 are defined herein, pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, for example, for treating a disease or condition mediated by TYK2 kinase in a patient.

  提供了一些噻唑吡啶化合物，这些化合物是TYK2激酶的抑制剂，包含这些化合物的组合物以及治疗由TYK2激酶介导的疾病的方法。具体来说，提供了符合Formula (I)、(II)或(III)的化合物，其立体异构体、互变异构体、溶剂合物、前药或其药用可接受的盐，其中X、R0、R1、R2、R3、R4和R5在此有定义，包括该化合物和药用可接受的载体、辅料或溶剂的药物组合物，使用该化合物或组合物进行治疗的方法，例如，用于治疗患有TYK2激酶介导的疾病或症状的患者。
• [EN] NOVEL FUSED CYCLIC COMPOUND AND USE THEREOF<br/>[FR] NOUVEAU COMPOSÉ CYCLIQUE FONDU ET SON UTILISATION
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010143733A1

  公开（公告）日：2010-12-16

  A compound represented by the formula (I): wherein each symbol is as defined in the specification, and a salt thereof have a GPR40 receptor activation action and is useful as an insulin secretagogue or a prophylactic or therapeutic drug for diabetes and the like.

  化合物的化学式为（I）：其中每个符号如规范中定义，其盐具有GPR40受体激活作用，并且可用作胰岛素分泌剂或糖尿病等的预防或治疗药物。