6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-one

• 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: 6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-one
• 英文别名: 6-[Amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol4-yl)-methyl]4-(3-chloro-phenyl)-1H-quinolin-2-one；6-[amino-(6-chloropyridin-3-yl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1H-quinolin-2-one
• 化学式: C₂₅H₁₉Cl₂N₅O
• 分子量: 476.365
• InChiKey: XQHDYAHKRUSHDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  85.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-one 、 羟胺 、 4-甲氧基苯甲醛 以 溶剂黄146 、 乙酸乙酯 为溶剂， 以78%的产率得到4-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-[(4-methoxy-benzylidene)-amino]-(3-methyl-3H-imidazol-4-yl)-methyl]-1H-quinolin-2-one
  参考文献：
  名称：

  Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents

  摘要：

  本发明涉及公式1的化合物及其药学上可接受的盐和溶剂化物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和Z的定义如本文所述。本发明还涉及包含公式1化合物的制药组合物，并通过向哺乳动物投与公式1化合物来抑制异常细胞生长，包括癌症的方法。本发明还涉及在合成公式1化合物中有用的中间体和方法。

  公开号：

  US06258824B1
• 作为产物：
  描述：

  [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanol 在 氯化亚砜 、 氨 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以88%的产率得到6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1H-quinolin-2-one
  参考文献：
  名称：

  Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents

  摘要：

  本发明涉及公式1的化合物及其药学上可接受的盐和溶剂化物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和Z的定义如本文所述。本发明还涉及包含公式1化合物的制药组合物，并通过向哺乳动物投与公式1化合物来抑制异常细胞生长，包括癌症的方法。本发明还涉及在合成公式1化合物中有用的中间体和方法。

  公开号：

  US06258824B1

文献信息

• QUINOLINONE FARNESYL TRANSFERASE INHIBITORS FOR THE TREATMENT OF SYNUCLEINOPATHIES AND OTHER INDICATIONS
  申请人：Lansbury, JR. Peter T.

  公开号：US20090253655A1

  公开（公告）日：2009-10-08

  Novel quinolinone farnesyl transferase inhibitors are provided. These new compounds are useful in the treatment or prevention of synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease, multiple system atrophy, and disorders of brain iron concentration including pantothenate kinase-associated neurodegeneration (e.g., PANK1), or other neurodegenerative/neurological diseases. Provided compounds are also useful in the treatment of proliferative diseases such as cancer, and in the treatment of neurological diseases, such as cognitive impairment, depression, and anxiety. The treatment including administering to a subject a therapeutically effective amount of an inventive farnesyl transferase inhibitor compound.

  提供了新型喹诺酮法尼西基转移酶抑制剂。这些新化合物在治疗或预防突触核蛋白病（如帕金森病、弥漫性莱维小体病、多系统萎缩和脑铁浓度紊乱疾病，包括泛酰辅酶A激酶相关的神经退行性疾病（例如PANK1）或其他神经退行性/神经系统疾病方面具有用处。提供的化合物还可用于治疗癌症等增生性疾病，以及治疗认知障碍、抑郁症和焦虑等神经系统疾病。治疗包括向受试者施用一种创新的法尼西基转移酶抑制剂化合物的治疗有效剂量。
• Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents
  申请人：Pfizer Inc.

  公开号：US06258824B1

  公开（公告）日：2001-07-10

  The present invention relates to compounds of formula 1 and pharmaceutically acceptable salts and solvates thereof wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and Z are as defined herein. The invention also relates to pharmaceutical compositions comprising compounds of formula 1 and to methods of inhibiting abnormal cell growth, including cancer, in a mammal by administering compounds of formula 1 to the mammal. The invention also relates to intermediates and methods useful in synthesizing compounds of formula 1.

  本发明涉及公式1的化合物及其药学上可接受的盐和溶剂化物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和Z的定义如本文所述。本发明还涉及包含公式1化合物的制药组合物，并通过向哺乳动物投与公式1化合物来抑制异常细胞生长，包括癌症的方法。本发明还涉及在合成公式1化合物中有用的中间体和方法。
• TREATMENT OF PROTEINOPATHIES USING A FARNESYL TRANSFERASE INHIBITOR
  申请人：Lansbury, JR. Peter T.

  公开号：US20110294794A1

  公开（公告）日：2011-12-01

  Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject in need thereof a therapeutically effective amount of a farnesyl transferase inhibitor, wherein the amount is effective to inhibit the farnesylation of a non-Ras FTase substrate involved in the autophagy pathway without substantially affecting the farnesylation of Ras or other oncology related substrates. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

  本发明提供了一种低剂量法尼醇转移酶抑制剂及其制药组合物，用于治疗蛋白病。这些低剂量低于最初设计这些化合物用于肿瘤治疗所使用的剂量。治疗包括向需要治疗的受体中注射治疗有效量的法尼醇转移酶抑制剂，其中该量能够有效抑制参与自噬通路的非Ras FTase底物的法尼酰化，而不会对Ras或其他与肿瘤相关的底物的法尼酰化产生明显影响。按照本发明的治疗方法还可以包括乙酰胆碱酯酶抑制剂、神经营养因子受体激活剂、NMDA拮抗剂、淀粉样沉积抑制剂、抗精神病药物、抗抑郁药物、抗焦虑药物或抗氧化剂。
• Treatment of synucleinopathies
  申请人：Link Medicine Corporation

  公开号：EP2545919A1

  公开（公告）日：2013-01-16

  Methods and compositions useful in the treatment or prevention of synucleinopathies, such as Parkinson's Disease, Diffuse Lewy Body Disease, and Multiple System Artophy, or other neurodegenerative diseases are provided. The treatment including administering to a subject a farnesyl transferase inhibitor compound.

  本研究提供了用于治疗或预防突触核蛋白病（如帕金森病、弥漫性路易体病和多系统阿尔茨海默病）或其他神经退行性疾病的方法和组合物。治疗方法包括向受试者施用法尼基转移酶抑制剂化合物。
• HETEROARYL-SUBSTITUTED QUINOLIN-2-ONE DERIVATIVES USEFUL AS ANTICANCER AGENTS
  申请人：Pfizer Products Inc.

  公开号：EP1150973A1

  公开（公告）日：2001-11-07