N-(2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1,3-thiazole-2-carboxamide | 764647-38-3

• 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: N-(2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1,3-thiazole-2-carboxamide
• CAS: 764647-38-3
• 化学式: C₁₄H₁₁N₅OS
• 分子量: 297.34
• InChiKey: VMXGPUCATDKJDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.64
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  69.95
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-(2-aminophenyl)-4,5-dihydro-1H-imidazole 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1,3-thiazole-2-carboxamide
  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

• 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 2,3-DIHYDROIMIDAZO[1,2-C]QUINAZOLINE-CONTAINING COMBINATIONS
  申请人：Liu Ningshu

  公开号：US20130184270A1

  公开（公告）日：2013-07-18

  The present invention relates to: combinations of: component A: one or more 2,3-dihydroimidazo[1,2-c]quinazoline compounds of general formula (A1) or (A2), or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; component B: one or more N-(2-arylamino)aryl sulfonamide compounds of general formula (B), or Lapatinib, or Paclitaxel, or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; and, optionally, component C: one or more further pharmaceutical agents; in which optionally some or all of the components are in the form of a pharmaceutical formulation which is ready for use to be administered simultaneously, concurrently, separately or sequentially. dependently of one another by the oral, intravenous, topical, local installations, intraperitoneal or nasal route; use of such combinations for the preparation of a medicament for the treatment or prophylaxis of a cancer; and a kit comprising such a combination.
• US7511041B2
  申请人：——

  公开号：US7511041B2

  公开（公告）日：2009-03-31
• US8129386B2
  申请人：——

  公开号：US8129386B2

  公开（公告）日：2012-03-06