N²-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-6-methyl-N⁸-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine | 1578244-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N²-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-6-methyl-N⁸-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine
• 英文别名: N2-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-6-methyl-N8-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine；8-N-(2,2-dimethylpropyl)-2-N-[2-methoxy-4-(1-methylpyrazol-4-yl)phenyl]-6-methylpyrido[3,4-d]pyrimidine-2,8-diamine
• CAS: 1578244-08-2
• 化学式: C₂₄H₂₉N₇O
• 分子量: 431.541
• InChiKey: WHILQXQBDZFLED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-甲基巯基-5-溴嘧啶-4-甲酸甲酯 在 copper(l) iodide 、 四(三苯基膦)钯 、 氨 、 sodium hydride 、 对甲苯磺酸 、 三乙胺 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 146.26h， 生成 N²-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-6-methyl-N⁸-neopentylpyrido[3,4-d]pyrimidine-2,8-diamine
  参考文献：
  名称：

  扩大融合嘧啶作为激酶抑制剂支架的范围：吡啶并[3,4-d]嘧啶的合成和修饰†

  摘要：

  融合的嘧啶核心是特殊的激酶支架，但在激酶抑制剂计划的背景下，很少有 2-氨基-吡啶并[3,4- d ]嘧啶化学型的例子被披露。此外，尚未报道获得 2-氨基-吡啶并[3,4- d ]嘧啶衍生物的通用合成路线。在这里，我们报告了一种针对此类分子的通用且有效的化学方法。我们的策略涉及8-氯-2-（甲硫基）吡啶并[3,4- d ]嘧啶中间体的简明制备及其有效衍生化，以得到具有激酶抑制剂潜力的新型化合物。

  DOI：

  10.1039/c4ob02238f

文献信息

• [EN] INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS
  申请人：CANCER REC TECH LTD

  公开号：WO2014037750A1

  公开（公告）日：2014-03-13

  The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式(I)的化合物，其中R、R、Ar、W、X和Z均如本文所定义。本发明的化合物已知可以通过直接或间接地与Mps1激酶本身相互作用来抑制单丝粒体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。具体而言，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。
• INHIBITOR COMPOUNDS
  申请人：CANCER RESEARCH TECHNOLOGY

  公开号：US20150239884A1

  公开（公告）日：2015-08-27

  The present invention relates to compounds of formula I wherein R 1 , R 4 , Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中R1、R4、Ar、W、X和Z均如本文所定义。本发明的化合物已知能够直接或间接地通过与Mps1激酶本身的相互作用来抑制单纺锤体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。特别地，本发明涉及使用这些化合物作为治疗和/或预防增生性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的过程，以及包含它们的药物组合物。
• Inhibitor compounds
  申请人：Cancer Research Technology Limited

  公开号：US09409907B2

  公开（公告）日：2016-08-09

  The present invention relates to compounds of formula I wherein R1, R4, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中R1、R4、Ar、W、X和Z的定义如本文所述。本发明的化合物已知可以直接或间接地通过与Mps1激酶本身的相互作用来抑制单纺锤体1（Mps1 - 也称为TTK）激酶的纺锤体检查点功能。特别地，本发明涉及使用这些化合物作为治疗和/或预防增生性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的过程，以及包含它们的药物组合物。
• N2-PHENYL-PYRIDO[3,4-D]PYRIMIDINE-2,8-DIAMINE DERIVATIVES AND THEIR USE AS MPS1 INHIBITORS
  申请人：Cancer Research Technology Limited

  公开号：EP3575299A1

  公开（公告）日：2019-12-04

  The present invention relates to compounds of formula I wherein R1, R2, R3 and R4 are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 - also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式 I 的化合物 其中 R1、R2、R3 和 R4 均如本文所定义。已知本发明的化合物可直接或通过与 Mps1 激酶本身的相互作用间接抑制 Monospindle 1（Mps1--也称为 TTK）激酶的纺锤体检查点功能。特别是，本发明涉及将这些化合物用作治疗和/或预防癌症等增殖性疾病的治疗剂。本发明还涉及这些化合物的制备工艺以及包含这些化合物的药物组合物。
• N2-phenyl-pyrido[3,4-D]pyrimidine-2, 8-diamine derivatives and their use as Mps1 inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US10399974B2

  公开（公告）日：2019-09-03

  The present invention relates to compounds of formula I: wherein R1, R2, R3 and R4 are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式 I 的化合物： 其中 R1、R2、R3 和 R4 均如本文所定义。已知本发明的化合物可直接或间接通过与 Mps1 激酶本身的相互作用抑制 Monospindle 1（Mps1--又称 TTK）激酶的纺锤体检查点功能。特别是，本发明涉及将这些化合物用作治疗和/或预防癌症等增殖性疾病的治疗剂。本发明还涉及这些化合物的制备工艺以及包含这些化合物的药物组合物。