N-(5-methyl-1H-pyrazol-3-yl)-2-pyridin-4-ylquinazolin-4-amine | 404828-10-0

• 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: N-(5-methyl-1H-pyrazol-3-yl)-2-pyridin-4-ylquinazolin-4-amine
• CAS: 404828-10-0
• 化学式: C₁₇H₁₄N₆
• 分子量: 302.338
• InChiKey: LGWDGIALCCNBQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基-5-甲基吡唑 、 4-氯-2-吡啶-4-喹唑啉 在 N,N-二甲基甲酰胺 作用下， 生成 N-(5-methyl-1H-pyrazol-3-yl)-2-pyridin-4-ylquinazolin-4-amine
  参考文献：
  名称：

  The discovery of the potent aurora inhibitor MK-0457 (VX-680)

  摘要：

  The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modi. cation of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) containing the T315I mutation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.136

文献信息

• Inhibitors of GSK-3 and crystal structures of GSK-3 protein and protein complexes
  申请人：——

  公开号：US20030125332A1

  公开（公告）日：2003-07-03

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3&bgr; or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3&bgr; protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3&bgr; protein or GSK-3&bgr; protein complexes.

  本发明涉及GSK-3的抑制剂及制备这些抑制剂的方法。本发明还提供了包含这些抑制剂的药物组合物，并提供了利用这些组合物在治疗和预防各种疾病，如糖尿病和阿尔茨海默病等方面的方法。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一种计算机，其包括一个数据存储介质，编码有这些结合口袋的结构坐标。本发明还涉及利用这些结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及利用这些结构坐标来筛选和设计能够结合到GSK-3β蛋白或其同源物的化合物的方法。本发明还涉及包含GSK-3β蛋白或GSK-3β蛋白复合物的可结晶组合物和晶体。
• Pyrazole compounds useful as protein kinase inhibitors
  申请人：——

  公开号：US20040224944A1

  公开（公告）日：2004-11-11

  This invention describes novel pyrazole compounds of formula IV: 1 wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; R x and R y are independently selected from T-R 3 , or taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen; and R 2 , R 2′ , T, and R 3 are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

  本发明描述了公式IV：1的新型吡唑化合物，其中环D是从芳基，杂芳基，杂环基或碳环基中选择的5-7成员单环或8-10成员双环。 Rx和Ry独立选择自T-R3，或者与它们之间的原子结合形成融合的，不饱和的或部分不饱和的5-8成员环，其中有1-3个环杂原子，所述的杂原子选择自氧，硫或氮。 R2，R2'，T和R3如说明书所述。这些化合物可用作蛋白激酶抑制剂，特别是作为aurora-2和GSK-3的抑制剂，用于治疗癌症，糖尿病和阿尔茨海默病等疾病。
• Triazole compounds useful as protein kinase inhibitors
  申请人：——

  公开号：US20040097501A1

  公开（公告）日：2004-05-20

  This invention describes novel triazole compounds of formula IX: 1 wherein Z 1 is nitrogen or CR 9 and Z 2 is nitrogen or CH, provided that at least one of Z 1 and Z 2 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from —R 1 ; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; R x and R y are independently selected from T-R 3 , or R x and R y are taken together with their intervening atoms to form a fused ring; R 1 , R 3 , and T are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of GSK-3 and Aurora, for treating diseases such as diabetes, cancer, and Alzheimer's disease.

  本发明描述了式IX的新型三唑类化合物：其中Z1是氮或CR9，Z2是氮或CH，但至少其中一个为氮；G为环C或环D；环C选自苯基、吡啶基、嘧啶基、吡嗪基、吡咯基或1,2,4-三嗪基环，其中所述环C具有一个或两个独立选择自—R1的邻位取代基；环D为选自芳基、杂芳基、杂环基或碳环基的5-7成员单环或8-10成员双环；Rx和Ry独立选择自T-R3，或Rx和Ry连同它们之间的原子形成融合环；R1、R3和T如说明书所述。该化合物可用作蛋白激酶抑制剂，特别是GSK-3和Aurora的抑制剂，用于治疗糖尿病、癌症和阿尔茨海默病等疾病。
• Inhibitors of GSK-3 and crystal structures of GSK-3beta protein and protein complexes
  申请人：ter Haar Ernst

  公开号：US20080262205A1

  公开（公告）日：2008-10-23

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其制备方法。本发明还提供了包含该抑制剂的药物组合物以及将这些组合物用于治疗和预防各种疾病，如糖尿病和阿尔茨海默病的方法。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一台计算机，该计算机包括编码有这些结合口袋的结构坐标的数据存储介质。本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标来筛选和设计与GSK-3β蛋白质或其同源物结合的化合物的方法。本发明还涉及包含GSK-3β蛋白质或GSK-3β蛋白质复合物的可结晶化组合物和晶体。
• INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3BETA PROTEIN AND PROTEIN COMPLEXES
  申请人：ter Haar Ernst

  公开号：US20100227814A1

  公开（公告）日：2010-09-09

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其制备方法。本发明还提供了包含该抑制剂的制药组合物，并提供了利用该组合物治疗和预防各种疾病，例如糖尿病和阿尔茨海默病的方法。此外，本发明还涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一种计算机，该计算机包括一个数据存储介质，该介质编码有这些结合口袋的结构坐标。本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标来筛选和设计与GSK-3β蛋白或其同源物结合的化合物的方法。本发明还涉及包含GSK-3β蛋白或GSK-3β蛋白复合物的可结晶组合物和晶体。