2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)-quinoline-4-carboxylic acid | 1259522-98-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)-quinoline-4-carboxylic acid
• 英文别名: 2-(1-(Tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid；6-fluoro-2-[1-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-3-pyridin-2-ylquinoline-4-carboxylic acid
• CAS: 1259522-98-9
• 化学式: C₂₂H₂₂FN₃O₄
• 分子量: 411.433
• InChiKey: AVOAWIMMQKTGOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)-quinoline-4-carboxylic acid 在 盐酸 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 1.5h， 生成 4-amino-6-(1-(6-fluoro-4-(piperazine-1-carbonyl)-3-(pyridin-2-yl)quinolin-2-yl)ethylamino)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Discovery and in Vivo Evaluation of the Potent and Selective PI3Kδ Inhibitors 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-0687) and 2-((1S)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-5-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-1430)

  摘要：

  Optimization of the potency and pharmacokinetic profile of 2,3,4-trisubstituted quinoline, 4, led to the discovery of two potent, selective, and orally bioavailable PI3K delta inhibitors, 6a (AM-0687) and 7 (AM-1430). On the basis of their improved profile, these analogs were selected for in vivo pharmacodynamic (PD) and efficacy experiments in animal models of inflammation. The in vivo PD studies, which were carried out in a mouse pAKT inhibition animal model, confirmed the observed potency of 6a and 7 in biochemical and cellular assays. Efficacy experiments in a keyhole limpet hemocyanin model in rats demonstrated that administration of either 6a or 7 resulted in a strong dose-dependent reduction of IgG and IgM specific antibodies. The excellent in vitro and in vivo profiles of these analogs make them suitable for further development.

  DOI：

  10.1021/acs.jmedchem.6b00827
• 作为产物：
  描述：

  碳酸甲丙酯 在 甲基锂 、 异丙基氯化镁 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 为溶剂， 反应 2.67h， 生成 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)-quinoline-4-carboxylic acid
  参考文献：
  名称：

  [EN] QUINOLINE DERIVATIVES AS PIK3 INHIBITORS
  [FR] DÉRIVÉS DE QUINOLÉINE EN TANT QU'INHIBITEURS DE PI3K

  摘要：

  具有通用公式（I）的取代的双环杂环芳基化合物及含有它们的组合物，用于治疗一般性炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠道疾病、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问题、慢性炎症性疾病，包括但不限于自身免疫性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、干燥综合征和自身免疫性溶血性贫血，包括所有形式的过敏症状。本发明还提供了治疗通过或与p1108活性介导、依赖或相关联的癌症的方法，包括但不限于白血病，如急性髓系白血病（AML）、骨髓增生异常综合征（MDS）、骨髓增殖性疾病（MPD）、慢性髓系白血病（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细胞淋巴瘤和固体肿瘤，如乳腺癌。

  公开号：

  WO2012068343A1

文献信息

• HETEROCYCLIC COMPOUNDS AND THEIR USES
  申请人：Bui Minna

  公开号：US20100331306A1

  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, Sjoegren'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，用于治疗一般性炎症、关节炎、风湿性疾病、骨关节炎、炎性肠道疾病、炎性眼部疾病、炎性或不稳定膀胱疾病、牛皮癣、具有炎症成分的皮肤疾病、慢性炎症症状，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、Sjogren综合症和自身免疫性溶血性贫血，包括各种过敏症状。本发明还提供了一种治疗与p110δ活性有关、依赖于或相关的癌症的方法，包括但不限于白血病，如急性髓细胞白血病（AML）、髓增生异常综合征（MDS）、髓增生性疾病（MPD）、慢性髓细胞白血病（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。
• Heterocyclic compounds and their uses
  申请人：Cushing Timothy David

  公开号：US08765768B2

  公开（公告）日：2014-07-01

  Substituted bicyclic heteroaryls having the general formula (I) 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, Sjoegren'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 p1 108 activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML), Myelodysplastic 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.

  具有通式（I）的替代双环杂芳基化合物及其组合物，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、炎症性眼病、炎症性或不稳定的膀胱疾病、银屑病、具有炎症成分的皮肤疾病、包括但不限于自身免疫性疾病，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，包括所有过敏形式的过敏症状。本发明还提供了治疗介导、依赖或与p1 108活性相关的癌症的方法，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）、非何杰金淋巴瘤（NHL）、B细胞淋巴瘤和实体瘤，如乳腺癌。
• POLYCYCLIC DERIVATIVES OF PYRIDINE AND THEIR USE IN THE TREATMENT OF (INTER ALIA) RHEUMATOID ARTHRITIS AND SIMILAR DISEASES
  申请人：Amgen, Inc

  公开号：EP2445900A2

  公开（公告）日：2012-05-02
• QUINOLINE DERIVATIVES AS PIK3 INHIBITORS
  申请人：Amgen Inc.

  公开号：EP2640715A1

  公开（公告）日：2013-09-25
• US8765768B2
  申请人：——

  公开号：US8765768B2

  公开（公告）日：2014-07-01