4-morpholin-4-yl-2-nitro-benzonitrile | 28340-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-morpholin-4-yl-2-nitro-benzonitrile
• 英文别名: 4-(morpholin-4-yl)-2-nitrobenzonitrile；4-morpholino-2-nitrobenzonitrile；2-Cyano-5-morpholino-chlorbenzol；2-Cyano-5-morpholino-nitrobenzol；2-Cyano-5-morpholinonitrobenzol；4-morpholin-4-yl-2-nitrobenzonitrile
• CAS: 28340-71-8
• 化学式: C₁₁H₁₁N₃O₃
• mdl: MFCD22047541
• 分子量: 233.227
• InChiKey: AHAKSKWSLHPGIM-UHFFFAOYSA-N

物化性质

• 熔点：
  194-195 °C(Solv: acetone (67-64-1))
• 沸点：
  467.5±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-morpholin-4-yl-2-nitro-benzonitrile 在 盐酸 、 tin(ll) chloride 作用下， 反应 6.5h， 生成 7-morpholin-4-yl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  环状胍。17.新型的（N-取代的氨基）咪唑并[2，1-b]喹唑啉-2：水溶性血小板凝集抑制剂。

  摘要：

  制备了一系列新型的被仲氨基取代的1,2,3,5-四氢咪唑并[2,1-b]喹唑啉-2-酮衍生物，并测试了其在体外和体外对大鼠血小板聚集的抑制作用。体内。发现大多数化合物是血小板聚集的有效抑制剂。一些活性化合物可溶于水，并通过静脉内输注对大鼠有效。结构活性关系表明，位于位置6或7的亲脂性仲氨基有助于保持有效活性。在研究的化合物中，最优选的化合物是7-哌啶子基-1,2,3,5-四氢咪唑并[2,1-b]喹唑啉-2-（13 g，DN-9693）。

  DOI：

  10.1021/jm00148a003
• 作为产物：
  描述：

  吗啉 、 2,4-二硝基苯甲腈 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以55%的产率得到4-morpholin-4-yl-2-nitro-benzonitrile
  参考文献：
  名称：

  环状胍。17.新型的（N-取代的氨基）咪唑并[2，1-b]喹唑啉-2：水溶性血小板凝集抑制剂。

  摘要：

  制备了一系列新型的被仲氨基取代的1,2,3,5-四氢咪唑并[2,1-b]喹唑啉-2-酮衍生物，并测试了其在体外和体外对大鼠血小板聚集的抑制作用。体内。发现大多数化合物是血小板聚集的有效抑制剂。一些活性化合物可溶于水，并通过静脉内输注对大鼠有效。结构活性关系表明，位于位置6或7的亲脂性仲氨基有助于保持有效活性。在研究的化合物中，最优选的化合物是7-哌啶子基-1,2,3,5-四氢咪唑并[2,1-b]喹唑啉-2-（13 g，DN-9693）。

  DOI：

  10.1021/jm00148a003

文献信息

• [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。
• HETEROCYCLIC COMPOUNDS AND THEIR USES
  申请人：Cushing Timothy D.

  公开号：US20100331293A1

  公开（公告）日：2010-12-30

  Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjogren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

  含有替代双环杂环芳基的化合物及其组合物，用于治疗一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定膀胱疾病、牛皮癣、具有炎症成分的皮肤疾病、慢性炎症性疾病，包括但不限于自身免疫疾病如系统性红斑狼疮（SLE）、重症肌无力、类风湿性关节炎、急性播散性脑脊髓炎、特发性血小板减少性紫癜、多发性硬化症、干燥综合征和自身免疫性溶血性贫血，包括各种过敏症状，本发明还提供了治疗与p110δ活性有关的、依赖于或与之相关的癌症的方法，包括但不限于白血病，如急性髓系白血病（AML）、髓增生异常综合征（MDS）、髓增生性疾病（MPD）、慢性髓性白血病（CML）、T细胞急性淋巴细胞白血病（T-ALL）、B细胞急性淋巴细胞白血病（B-ALL）、非霍奇金淋巴瘤（NHL）、B细胞淋巴瘤和实体肿瘤，如乳腺癌。
• Fused azole-pyrimidine derivatives
  申请人：Shimada Mitsuyuki

  公开号：US20060128732A1

  公开（公告）日：2006-06-15

  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 (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, 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 PI3K activity in a human or animal subject.

  本发明涉及杂环融合的唑啉嘧啶衍生物，以及制备它们的方法和含有它们的制药制剂。本发明的杂环融合的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PI3K-γ抑制活性，并可用于预防和治疗与PI3K和特别是PI3K-γ活性相关的疾病。更具体地说，本发明的唑啉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、心肌收缩力障碍、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、肾功能衰竭、心脏肥大，以及神经退行性疾病，如帕金森病、阿尔茨海默病、糖尿病和局部缺血，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：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。
• Quinoline derivitives and their uses
  申请人：Cushing Timothy D.

  公开号：US08940724B2

  公开（公告）日：2015-01-27

  Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjogren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

  含有替代双环杂芳基的化合物及其组合物，用于治疗一般性炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、伴有炎症成分的皮肤疾病、包括但不限于自身免疫疾病，如系统性红斑狼疮（SLE）、重症肌无力、类风湿性关节炎、急性播散性脑脊髓炎、特发性血小板减少性紫癜、多发性硬化症、Sjogren综合征和自身免疫性溶血性贫血，包括所有形式的过敏反应。本发明还提供了治疗与p110δ活性相关、依赖或关联的癌症的方法，包括但不限于白血病，如急性髓性白血病（AML）、骨髓增生异常综合征（MDS）、骨髓增生性疾病（MPD）、慢性髓性白血病（CML）、T细胞急性淋巴细胞白血病（T-ALL）、B细胞急性淋巴细胞白血病（B-ALL）、非霍奇金淋巴瘤（NHL）、B细胞淋巴瘤和实体瘤，如乳腺癌。