2-chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine | 404828-30-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine
• CAS: 404828-30-4
• 化学式: C₁₂H₁₀ClN₅
• 分子量: 259.698
• InChiKey: GWEOBKYRGURQCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  450.2±45.0 °C(Predicted)
• 密度：
  1.477±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 正丁醇 为溶剂， 反应 24.0h， 生成 N2-methyl-N4-(5-methyl-1H-pyrazol-3-yl)-N2-(octahydrocyclopenta[c]pyrrol-5-yl)quinazoline-2,4-diamine
  参考文献：
  名称：

  取代的杂芳基化合物及其组合物和用途

  摘要：

  本发明提供了一类取代的杂芳基化合物及其组合物和它们的用途。所述的化合物为式(I)所示的化合物或式(I)所示化合物的立体异构体、互变异构体、氮氧化物、溶剂化物、代谢产物、药学上可接受的盐或它的前药。本发明还提供了包含所述化合物的药物组合物，所述的化合物和药物组合物可以调节JAK激酶的活性，用于预防、处理、治疗和减轻JAK激酶介导的疾病或紊乱。

  公开号：

  CN105367555B
• 作为产物：
  描述：

  2,4-喹唑啉二酮 在 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基苯胺 为溶剂， 生成 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine
  参考文献：
  名称：

  Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis

  摘要：

  A high-throughput screen against PknB, an essential serine-threonine protein kinase present in Mycobacterium tuberculosis (M. tuberculosis), allowed the identification of an aminoquinazoline inhibitor which was used as a starting point for SAR investigations. Although a significant improvement in enzyme affinity was achieved, the aminoquinazolines showed little or no cellular activity against M. tuberculosis. However, switching to an aminopyrimidine core scaffold and the introduction of a basic amine side chain afforded compounds with nanomolar enzyme binding affinity and micromolar minimum inhibitory concentrations against M. tuberculosis. Replacement of the pyrazole head group with pyridine then allowed equipotent compounds with improved selectivity against a human kinase panel to be obtained. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.107

文献信息

• 稠环化合物、包含其的药物组合物及其制备方法和用途
  申请人：四川科伦博泰生物医药股份有限公司

  公开号：CN111285882B

  公开（公告）日：2022-12-02

  本发明涉及式(I‑A)或式(I‑B)的稠环化合物、包含其的药物组合物、其制备方法及其用于预防或治疗与RET活性相关的疾病或病况。
• Pyrazole compounds useful as protein kinase inhibitors
  申请人：Bebbington David

  公开号：US20050038023A1

  公开（公告）日：2005-02-17

  This invention describes novel pyrazole compounds of formula IIIa: wherein R 1 is T-Ring D, 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 , R y , R 2 ; and R 2′ 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.

  这项发明描述了公式IIIa的新型吡唑化合物：其中R1是T-Ring D，其中环D是选择自芳基、杂芳基、杂环基或碳环基的5-7成员单环或8-10成员双环环；Rx、Ry、R2和R2'如规范中描述。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。
• Pyrazole compounds useful as protein kinase inhititors
  申请人：——

  公开号：US20030004161A1

  公开（公告）日：2003-01-02

  This invention describes novel pyrazole compounds of formula I′: 1 wherein Q′ is —O—, —C(R 6′ ) 2 —, 1,2-cyclopropanediyl, 1,2-cyclobutanediyl, or 1,3-cyclopropanediyl, and R 1 is T-Ring D, 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 L-Z-R 3 or R x and R y are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-7 membered ring having 0-3 heteroatoms; and R 2 and R 2′ 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.

  这项发明描述了一种新颖的吡唑类化合物，化学式为I′:1其中Q′为—O—、—C(R6′)2—、1,2-环丙烷二基、1,2-环丁烷二基或1,3-环丙烷二基，R1为T-Ring D，其中Ring D为从芳香族、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分别独立选择自T-R3或L-Z-R3或Rx和Ry与它们之间的原子结合形成融合、不饱和或部分不饱和、含有0-3个杂原子的5-7成员环；R2和R2′如规范中描述。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。
• Design, synthesis and evaluation of N2,N4-diaminoquinazoline based inhibitors of phosphodiesterase type 5
  作者：Nattakarn Pobsuk、Tamkeen Urooj Paracha、Nattiya Chaichamnong、Nattapas Salaloy、Praphasri Suphakun、Supa Hannongbua、Kiattawee Choowongkomon、Dumrongsak Pekthong、Krongkarn Chootip、Kornkanok Ingkaninan、M. Paul Gleeson

  DOI：10.1016/j.bmcl.2018.11.043

  日期：2019.1

  We describe the design, synthesis and evaluation of a series of N2,N4-diaminoquinazoline analogs as PDE5 inhibitors. Twenty compounds were prepared and these were assessed in terms of their PDE5 and PDE6 activity, ex-vivo vasodilation response, mammalian cytotoxicity and aqueous solubility. Molecular docking was used to determine the binding mode of the series and this was demonstrated to be consistent

  我们描述了一系列作为PDE5抑制剂的N 2，N 4-二氨基喹唑啉类似物的设计，合成和评估。制备了二十种化合物，并根据它们的PDE5和PDE6活性，离体血管舒张反应，哺乳动物细胞毒性和水溶性对其进行了评估。分子对接用于确定该系列的结合模式，这被证明与观察到的SAR一致。化合物15是活性最高的PDE5抑制剂（IC 50  = 0.072±0.008 µM），选择性是PDE6的4.6倍。大鼠肺动脉血管舒张模型中离体评估15和22显示EC 50分别为1.63±0.72 µM和2.28±0.74 µM。
• 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。