imidazo[1,2-c]quinazolin-5-amine | 777057-13-3

• 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: imidazo[1,2-c]quinazolin-5-amine
• CAS: 777057-13-3
• 化学式: C₁₀H₈N₄
• 分子量: 184.2
• InChiKey: VRNQEIBRGYRAPD-UHFFFAOYSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  烟酸 、 imidazo[1,2-c]quinazolin-5-amine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以20%的产率得到N-imidazo[1,2-c]quinazolin-5-ylnicotinamide
  参考文献：
  名称：

  新型2,3-二氢咪唑并[1,2-c]喹唑啉PI3K抑制剂的发现和合成孔径雷达：鉴定帕潘替尼（BAY 80-6946）

  摘要：

  磷酸肌醇3激酶（PI3K）途径在许多疾病状态中都被异常激活，包括肿瘤细胞，无论是通过生长因子受体酪氨酸激酶还是通过关键途径成分的基因突变和扩增。多种PI3K亚型在癌症中起着不同的作用。因此，从新型化合物类别开发PI3K抑制剂应导致不同的药理和药代动力学特征，并允许探索各种适应症，组合和给药方案。旨在鉴定用于治疗炎性疾病的PI3Kγ抑制剂的筛选工作导致发现了新型2,3-二氢咪唑[1,2- c喹唑啉类的PI3K抑制剂。随后针对癌症治疗的前导优化程序着重于抑制PI3Kα和PI3Kβ。在此，描述了此类的初始结构-活性关系发现以及优化方法，该方法导致将copanlisib（BAY 80-6946）鉴定为治疗实体瘤和血液肿瘤的临床候选药物。

  DOI：

  10.1002/cmdc.201600148
• 作为产物：
  描述：

  2-(2-aminophenyl)-4,5-dihydro-1H-imidazole 在 N,N-二甲基丙烯基脲 、 manganese(IV) oxide 作用下， 以 甲醇 为溶剂， 生成 imidazo[1,2-c]quinazolin-5-amine
  参考文献：
  名称：

  新型2,3-二氢咪唑并[1,2-c]喹唑啉PI3K抑制剂的发现和合成孔径雷达：鉴定帕潘替尼（BAY 80-6946）

  摘要：

  磷酸肌醇3激酶（PI3K）途径在许多疾病状态中都被异常激活，包括肿瘤细胞，无论是通过生长因子受体酪氨酸激酶还是通过关键途径成分的基因突变和扩增。多种PI3K亚型在癌症中起着不同的作用。因此，从新型化合物类别开发PI3K抑制剂应导致不同的药理和药代动力学特征，并允许探索各种适应症，组合和给药方案。旨在鉴定用于治疗炎性疾病的PI3Kγ抑制剂的筛选工作导致发现了新型2,3-二氢咪唑[1,2- c喹唑啉类的PI3K抑制剂。随后针对癌症治疗的前导优化程序着重于抑制PI3Kα和PI3Kβ。在此，描述了此类的初始结构-活性关系发现以及优化方法，该方法导致将copanlisib（BAY 80-6946）鉴定为治疗实体瘤和血液肿瘤的临床候选药物。

  DOI：

  10.1002/cmdc.201600148

文献信息

• [EN] IMIDAZO [1,2-C] QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES<br/>[FR] COMPOSÉS IMIDAZO[1,2-C]QUINAZOLIN-5-AMINE PRÉSENTANT DES PROPRIÉTÉS ANTAGONISTES DU A2A
  申请人：MERCK SHARP & DOHME

  公开号：WO2019118313A1

  公开（公告）日：2019-06-20

  Disclosed are compounds having the structure of Formula I, or a pharmaceutically acceptable salt of any thereof: wherein: "Z" and R1 are defined herein, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.

  本文披露了具有Formula I结构的化合物，或者其任何药学上可接受的盐：其中：“Z”和R1在此有定义，这些化合物被认为适用于选择性拮抗A2a受体，例如，在基底神经节中高密度发现的受体。据信，这些化合物和药物配方在治疗或管理神经退行性疾病，例如帕金森病，或由于使用治疗或管理帕金森病的某些药物而引起的运动障碍方面是有用的。
• [EN] FUSED AZOLE-PYRIMIDINE DERIVATIVES<br/>[FR] DERIVES D'AZOLE-PYRIMIDINES FONDUES
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004029055A1

  公开（公告）日：2004-04-08

  The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (P13K) inhibition, especially for PI3K-Ϝ inhibition and can be used for the prophylaxis and treatment of diseases associated with P13K and particularly with P13K-Ϝ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to P13K activity in a human or animal subject.

  本发明涉及杂环嘧啶衍生物，其制备方法以及含有它们的药物制剂。本发明的杂环嘧啶衍生物对磷脂酰肌醇-3-激酶（PI3K）抑制具有增强的效力，尤其对PI3K-Ϝ抑制效果显著，可用于预防和治疗与PI3K以及特别是PI3K-Ϝ活性相关的疾病。具体而言，本发明的杂环衍生物可用于治疗和预防以下疾病：炎症和免疫调节性疾病，如哮喘、特应性皮炎、鼻炎、过敏性疾病、慢性阻塞性肺病（COPD）、脓毒性休克、关节疾病、风湿性关节炎、Graves病、癌症、心肌收缩功能障碍、心力衰竭、血栓栓塞、缺血和动脉粥样硬化。本发明的化合物还可用于肺动脉高压、肾功能衰竭、心肌肥大，以及神经退行性疾病，如帕金森病、阿尔茨海默病、糖尿病和局灶性缺血，因为这些疾病也与人类或动物主体的PI3K活性有关。
• FUSED AZOLE-PYRIMIDINE DERIVATIVES
  申请人：Shimada Mitsuyuki

  公开号：US20090270388A1

  公开（公告）日：2009-10-29

  The present invention relates to novel fused azolepyriimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoimmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.

  本发明涉及新型的融合式唑啉嘧啶衍生物、其制备方法和含有它们的药物制剂。本发明的融合式唑啉嘧啶衍生物表现出增强的磷脂酰肌醇-3-激酶（PI3K）抑制活性，特别是对PI3K-γ的抑制活性，可用于预防和治疗与PI3K，特别是PI3K-γ活性相关的疾病。更具体地说，本发明的唑啉嘧啶衍生物可用于以下疾病的治疗和预防：炎症和免疫调节性疾病，如哮喘、特应性皮炎、鼻炎、过敏疾病、慢性阻塞性肺疾病（COPD）、感染性休克、关节疾病、类风湿性关节炎和格雷夫斯病、癌症、心肌收缩功能障碍、心力衰竭、血栓栓塞、缺血和动脉硬化。本发明的化合物还可用于肺动脉高压、肾衰竭、心脏肥大，以及神经退行性疾病，如帕金森病、阿尔茨海默病、糖尿病和局灶性缺血，因为这些疾病也与人类或动物主体中的PI3K活性有关。
• Fused azole-pyrimidine derivatives
  申请人：Bayer HealthCare AG

  公开号：EP2042504A1

  公开（公告）日：2009-04-01

  The present invention relates to novel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoimmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.

  本发明涉及新型融合唑嘧啶衍生物、其制备工艺以及含有这些衍生物的药物制剂。本发明的融合唑嘧啶衍生物具有更强的磷脂酰肌醇-3-激酶（PI3K）抑制效力，特别是对 PI3K-γ 的抑制效力，可用于预防和治疗与 PI3K，特别是与 PI3K-γ 活性相关的疾病。 更具体地说，本发明的唑衍生物可用于治疗和预防以下疾病：炎症和免疫调节紊乱，如哮喘、特应性皮炎、鼻炎、过敏性疾病、慢性阻塞性肺病（COPD）、脓毒性休克、关节疾病、自身免疫性病变，如类风湿性关节炎和巴塞杜氏病、癌症、心肌收缩力紊乱、心力衰竭、血栓栓塞、缺血和动脉粥样硬化。 本发明的化合物还可用于肺动脉高压、肾功能衰竭、心肌肥大以及神经退行性疾病，如帕金森病、阿尔茨海默病、糖尿病和局灶性缺血，因为这些疾病也与人或动物体内的 PI3K 活性有关。
• Substituted imidazo[1,2-c]quinazolines as A2A antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US11498923B2

  公开（公告）日：2022-11-15

  Disclosed are compounds having the structure of Formula I, or a pharmaceutically acceptable salt of any thereof: wherein: “Z” and R1 are defined herein, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.

  所公开的是具有式 I 结构的化合物或其中任何一种的药学上可接受的盐：其中：Z "和 R1 在本文中定义，这些化合物被认为适用于选择性拮抗 A2a 受体，例如基底神经节中高密度存在的 A2a 受体。此类化合物和药物制剂被认为可用于治疗或控制神经退行性疾病，例如帕金森病，或因使用某些用于治疗或控制帕金森病的药物而引起的运动障碍。