5-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-2-amine | 1374635-54-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-2-amine
• 英文别名: Rel-5-((2S,6R)-2,6-dimethylmorpholino)pyridin-2-amine；5-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-2-amine
• CAS: 1374635-54-7
• 化学式: C₁₁H₁₇N₃O
• 分子量: 207.275
• InChiKey: HJSSTXGDOIYXFL-DTORHVGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  51.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-2-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-(二环己基膦)3,6-二甲氧基-2′,4′,6′-三异丙基-1,1′-联苯 、 caesium carbonate 、 三氟乙酸 作用下， 以 甲苯 、 叔丁醇 为溶剂， 反应 12.0h， 生成 N-(5-(2,6-dimethylmorpholino)pyridin-2-yl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridin-6-amine
  参考文献：
  名称：

  Antimalarial Lead-Optimization Studies on a 2,6-Imidazopyridine Series within a Constrained Chemical Space To Circumvent Atypical Dose–Response Curves against Multidrug Resistant Parasite Strains

  摘要：

  A lead-optimization program around a 2,6-imidazopyridine scaffold was initiated based on the two early lead compounds, 1 and 2, that were shown to be efficacious in an in vivo humanized Plasmodium falciparum NODscidIL2R gamma null mouse malaria infection model. The observation of atypical dose-response curves when some compounds were tested against multidrug resistant malaria parasite strains guided the optimization process to define a chemical space that led to typical sigmoidal dose-response and complete kill of multidrug resistant parasites. After a structure and property analysis identified such a chemical space, compounds were prepared that displayed suitable activity, ADME, and safety profiles with respect to cytotoxicity and hERG inhibition.

  DOI：

  10.1021/acs.jmedchem.8b01333
• 作为产物：
  描述：

  5-氟-2-硝基吡啶 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 40.0h， 生成 5-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-2-amine
  参考文献：
  名称：

  Antimalarial Lead-Optimization Studies on a 2,6-Imidazopyridine Series within a Constrained Chemical Space To Circumvent Atypical Dose–Response Curves against Multidrug Resistant Parasite Strains

  摘要：

  A lead-optimization program around a 2,6-imidazopyridine scaffold was initiated based on the two early lead compounds, 1 and 2, that were shown to be efficacious in an in vivo humanized Plasmodium falciparum NODscidIL2R gamma null mouse malaria infection model. The observation of atypical dose-response curves when some compounds were tested against multidrug resistant malaria parasite strains guided the optimization process to define a chemical space that led to typical sigmoidal dose-response and complete kill of multidrug resistant parasites. After a structure and property analysis identified such a chemical space, compounds were prepared that displayed suitable activity, ADME, and safety profiles with respect to cytotoxicity and hERG inhibition.

  DOI：

  10.1021/acs.jmedchem.8b01333

文献信息

• [EN] COMBINATIONS AND DOSING REGIMES TO TREAT RB-POSITIVE TUMORS<br/>[FR] COMBINAISONS ET RÉGIMES POSOLOGIQUES POUR TRAITER DES TUMEURS RB-POSITIVES
  申请人：G1 THERAPEUTICS INC

  公开号：WO2016040858A1

  公开（公告）日：2016-03-17

  This invention directed to methods for treating select RB-positive cancers and other Rb- positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.

  这项发明涉及使用特定剂量和组合或交替方案中的CDK4/6抑制剂治疗选择性RB阳性癌症和其他RB阳性异常细胞增殖紊乱疾病的方法。在一个方面，揭示了使用特定CDK4/6抑制剂与另一种化疗药物（例如，额外的激酶抑制剂、PD-1抑制剂或BCL-2抑制剂，或其组合）组合或交替治疗选择性RB阳性癌症。
• IMIDAZO[1',2':1,6]PYRIDO[2,3-D]PYRIMIDINE COMPOUND AS PROTEIN KINASE INHIBITOR
  申请人：SHENGKE PHARMACEUTICALS (JIANGSU) LTD.

  公开号：US20200270251A1

  公开（公告）日：2020-08-27

  Provided is an imidazo[1′;2′:1,6]pyrido[2,3-d]pyrimidine compound of general formula (I). The compound can be used in treating a cell proliferative disorder and is a cyclin-dependent kinase (CDK) inhibitor with broad-spectrum and strong activity.

  提供的是一种通式为(I)的咪唑[1′;2′:1,6]吡啶[2,3-d]嘧啶化合物。该化合物可用于治疗细胞增殖紊乱，是一种具有广谱和强活性的周期蛋白依赖性激酶（CDK）抑制剂。
• HETEROCYCLIC COMPOUND
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20160159773A1

  公开（公告）日：2016-06-09

  The present invention provides an agent for the prophylaxis or treatment of autoimmune diseases (e.g., psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus etc.) and the like, which has a superior Tyk2 inhibitory action. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种用于预防或治疗自身免疫性疾病（例如牛皮癣、类风湿关节炎、炎症性肠病、干燥综合征、贝赫切特病、多发性硬化症、系统性红斑狼疮等）等的药剂，其具有优越的Tyk2抑制作用。 本发明涉及一种由下式表示的化合物 其中每个符号如规范中定义的，或其盐。
• Design, synthesis, and biological evaluation of structurally modified isoindolinone and quinazolinone derivatives as hedgehog pathway inhibitors
  作者：Deepak Bhattarai、Joo Hyun Jung、Seunghyeon Han、Hankyu Lee、Soo Jin Oh、Hyuk Wan Ko、Kyeong Lee

  DOI：10.1016/j.ejmech.2016.10.040

  日期：2017.1

  structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biologically evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells. Compounds 9–11 and 14 with isoindolinone scaffolds demonstrated moderate Hh inhibitory activity; whereas quinazolinone derivatives 24, 29, 32, 34, and 35 exhibited good potency

  刺猬（Hh）信号通路与细胞事件的各个方面相关，例如整个胚胎发育和组织模式中的细胞迁移，增殖和分化。异常的Hh信号通路与许多人类癌症相关，包括基底细胞癌（BCC），髓母细胞瘤（MB），肺癌，前列腺癌和卵巢癌，因此它是癌症治疗中有希望的靶标。使用结构跳跃方法，我们设计了具有异吲哚啉酮或喹唑啉酮基团的新型Hh信号通路抑制剂，这些抑制剂已合成并在NIH3T3细胞中使用8xGli-萤光素酶（Gli-Luc）报告基因检测法进行了生物学评估。化合物9 – 11和14异吲哚啉酮支架具有中等的Hh抑制活性。而喹唑啉酮衍生物24，29，32，34，和35显示出良好的效力与亚微摩尔的IC 50值和模拟28显示纳摩尔IC 50值。尽管sonidegib对赋予vismodegib耐药性的Smo突变体显示出抑制作用的降低，但结构修饰的新化合物不仅具有Hh途径抑制作用的药效学特性，而且还保留了对耐药Smo突变体的抑制作
• CDK INHIBITORS
  申请人：G1 THERAPEUTICS, INC.

  公开号：US20130237534A1

  公开（公告）日：2013-09-12

  Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.

  式I、II或III的化合物及其药用盐可用作CDK抑制剂。