4-(4-甲基哌啶-1-基)苯胺 | 342013-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(4-甲基哌啶-1-基)苯胺
• 中文别名: 4-(4-甲基-哌啶-1-基)-苯基胺
• 英文名称: 4-(4-methylpiperidin-1-yl)aniline
• CAS: 342013-25-6
• 化学式: C₁₂H₁₈N₂
• mdl: MFCD01788290
• 分子量: 190.288
• InChiKey: UZQJQJNKYMSTCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-(4-甲基哌啶-1-基)苯胺 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 正丁醇 为溶剂， 50.0~90.0 ℃ 、101.33 kPa 条件下， 反应 11.0h， 生成 4-N-cyclopentyl-2-N-[4-(4-methylpiperidin-1-yl)phenyl]pyrimidine-2,4,5-triamine
  参考文献：
  名称：

  Structural Optimization and Structure–Activity Relationships of N²-(4-(4-Methylpiperazin-1-yl)phenyl)-N⁸-phenyl-9H-purine-2,8-diamine Derivatives, a New Class of Reversible Kinase Inhibitors Targeting both EGFR-Activating and Resistance Mutations

  摘要：

  This paper describe the structural optimization of a hit compound, N-2-(4-(4-methylpiperazin-1-yl)phenyl)-N-8-phenyl-9H-purine-2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclopentyl-N-2-(4-(4-methylpiperazin-1-yl)phenyl)-N-8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations, respectively. Compound 9e was further assessed for potency and selectivity in enzymatic assays and in vivo anti-NSCLC studies. The results indicated that compound 9e is a highly potent kinase inhibitor against both EGFR-activating and resistance mutations and has good kinase spectrum selectivity across the kinome. In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and complete tumor regression in a HCC827 xenograft model, and an oral dose of 50 mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.

  DOI：

  10.1021/jm301365e
• 作为产物：
  描述：

  4-甲基哌啶 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-(4-甲基哌啶-1-基)苯胺
  参考文献：
  名称：

  新型2,4-二氨基嘧啶衍生物作为有效的抗肿瘤药的设计，合成和生物学评估†

  摘要：

  为了开发具有抗癌活性的新型治疗剂，设计并合成了两个系列的具有三唑哌嗪或1,4,8-三氮杂螺[4.5] decan-3-one支架的新型2,4-二氨基嘧啶衍生物。初步研究表明，与palbociclib和momelotinib相比，某些化合物对四种测试的癌细胞系表现出中等至优异的效力。特别是，最有前途的化合物9k和13f在IC 50中显示出最有效的抗肿瘤活性分别针对A549，HCT-116，PC-3和MCF-7细胞系的2.14 / 1.98μM，3.59 / 2.78μM，5.52 / 4.27μM和3.69 / 4.01μM值。基于芳香环和嘧啶核上末端苯胺部分的变化，进行了结构-活性关系（SAR）研究。此外，通过进一步探索其生物活性，阐明了其抗癌活性的机制。结果表明，化合物9k明显抑制A549细胞系的增殖，导致线粒体膜电位大大降低，导致癌细胞凋亡，抑制肿瘤细胞迁移并延长A549细胞周期分布，表示在G2处受阻-M期，在S期积累。

  DOI：

  10.1039/c9nj02154j

文献信息

• [EN] CYCLIN-DEPENDENT KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES CYCLINE-DÉPENDANTES
  申请人：SPV THERAPEUTICS INC

  公开号：WO2020140055A1

  公开（公告）日：2020-07-02

  Described herein are compounds and their pharmaceutically acceptable salts, pharmaceutical compositions thereof, methods of treatment, and medical uses. The compounds described herein are modulators of cyclin-dependent kinases, and are useful in the treatment or alleviation of protein kinase associated disorders, including cancer, infectious diseases, autoimmune diseases, or cardiovascular diseases.

  本文描述了化合物及其药用盐，以及它们的药物组合物，治疗方法和医疗用途。本文描述的化合物是细胞周期依赖性激酶的调节剂，并且在治疗或缓解蛋白激酶相关疾病方面具有用途，包括癌症，传染病，自身免疫疾病或心血管疾病。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASE
  申请人：NUVATION BIO INC

  公开号：WO2021003314A1

  公开（公告）日：2021-01-07

  Heterocyclic compounds as CDK4 or CDK6 or other CDK inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.

  提供异环化合物作为CDK4或CDK6或其他CDK抑制剂。这些化合物可能作为治疗疾病的治疗剂，特别是在肿瘤学方面可能具有特殊用途。
• [EN] BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES À TITRE DE MODULATEURS DE MNK1 ET MNK2 ET LEURS UTILISATIONS
  申请人：AGENCY SCIENCE TECH & RES

  公开号：WO2013147711A1

  公开（公告）日：2013-10-03

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

  本发明涉及某些化合物（例如咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），这些化合物作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于预防和治疗疾病（例如增生性疾病（例如癌症）、炎症性疾病、阿尔茨海默病）的药物的用途，以及治疗这些疾病的方法。
• BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF
  申请人：Agency for Science, Technology and Research

  公开号：US20140371199A1

  公开（公告）日：2014-12-18

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

  本发明涉及某些化合物（例如咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），这些化合物作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于预防和治疗疾病（例如增生性疾病（例如癌症）、炎症性疾病、阿尔茨海默病）的药物的用途，以及治疗这些疾病的方法。
• PDE 10a Inhibitors for the Treatment of Type II Diabetes
  申请人：Janssen Pharmaceutica, NV

  公开号：US20140364413A1

  公开（公告）日：2014-12-11

  Disclosed are compounds, compositions and methods for treating Type II diabetes. Such compounds are represented by Formula (I) as follows: wherein R 1 , R 2 , L, and Q are defined herein.

  揭示了用于治疗2型糖尿病的化合物、组合物和方法。这些化合物由以下式（I）表示： 其中R1、R2、L和Q在此处定义。