2-((1S)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide | 1259522-94-5

• 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-((1S)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide
• 英文别名: AM-0687；(S)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-6-fluoro-N-methyl-3-(pyridin-2-yl)quinoline-4-carboxamide；2-[(1S)-1-[(6-amino-5-cyanopyrimidin-4-yl)amino]ethyl]-6-fluoro-N-methyl-3-pyridin-2-ylquinoline-4-carboxamide
• CAS: 1259522-94-5
• 化学式: C₂₃H₁₉FN₈O
• 分子量: 442.455
• InChiKey: OLJXUPJOUSFYSX-LBPRGKRZSA-N

物化性质

• 沸点：
  721.0±60.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-6-fluoro-N-methyl-3-(pyridin-2-yl)quinoline-4-carboxamide 生成 2-((1S)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-N-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide
  参考文献：
  名称：

  HETEROCYCLIC COMPOUNDS AND THEIR USES

  摘要：

  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。

  公开号：

  US20100331306A1

文献信息

• Discovery and in Vivo Evaluation of the Potent and Selective PI3Kδ Inhibitors 2-((1<i>S</i>)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-6-fluoro-<i>N</i>-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-0687) and 2-((1<i>S</i>)-1-((6-Amino-5-cyano-4-pyrimidinyl)amino)ethyl)-5-fluoro-<i>N</i>-methyl-3-(2-pyridinyl)-4-quinolinecarboxamide (AM-1430)
  作者：Felix Gonzalez-Lopez de Turiso、Xiaolin Hao、Youngsook Shin、Minna Bui、Iain D. G. Campuzano、Mario Cardozo、Michelle C. Dunn、Jason Duquette、Benjamin Fisher、Robert S. Foti、Kirk Henne、Xiao He、Yi-Ling Hu、Ron C. Kelly、Michael G. Johnson、Brian S. Lucas、John McCarter、Lawrence R. McGee、Julio C. Medina、Daniela Metz、Tisha San Miguel、Deanna Mohn、Thuy Tran、Christine Vissinga、Sharon Wannberg、Douglas A. Whittington、John Whoriskey、Gang Yu、Leeanne Zalameda、Xuxia Zhang、Timothy D. Cushing

  DOI：10.1021/acs.jmedchem.6b00827

  日期：2016.8.11

  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.
• 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：EP2445900B1

  公开（公告）日：2016-03-02
• US9873704B2
  申请人：——

  公开号：US9873704B2

  公开（公告）日：2018-01-23