1,6-萘啶-8-羧酸 | 362606-19-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 1,6-萘啶-8-羧酸
• 英文名称: 1,6-naphthyridine-8-carboxylic acid
• CAS: 362606-19-7
• 化学式: C₉H₆N₂O₂
• mdl: MFCD09863867
• 分子量: 174.159
• InChiKey: WERVZPSGADOFEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-amine 、 1,6-萘啶-8-羧酸 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling

  摘要：

  Disruption of interleukin-13 (IL-13) signaling with large molecule antibody therapies has shown promise in diseases of allergic inflammation. Given that IL-13 recruits several members of the Janus Kinase family (JAK1, JAK2, and TYK2) to its receptor complex, JAK inhibition may offer an alternate small molecule approach to disrupting IL-13 signaling. Herein we demonstrate that JAK1 is likely the isoform most important to IL-13 signaling. Structure-based design was then used to improve the JAK1 potency of a series of previously reported JAK2 inhibitors. The ability to impede IL-13 signaling was thereby significantly improved, with the best compounds exhibiting single digit nM IC50's in cell-based assays dependent upon IL-13 signaling. Appropriate substitution was further found to influence inhibition of a key off-target, LRRK2. Finally, the most potent compounds were found to be metabolically labile, which makes them ideal scaffolds for further development as topical agents for IL-13 mediated diseases of the lungs and skin (for example asthma and atopic dermatitis, respectively).

  DOI：

  10.1016/j.bmcl.2019.04.008

文献信息

• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102303A1

  公开（公告）日：2020-04-02

  Fused compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. Wherein R 1 , R 2 , R 2a , R 3 , R 3a , R 4 , and R 4a are defined herein.

  化合物的结构式（I）和结构式（II），含有它们的药物组合物，制备它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、紊乱和病况的方法，例如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、治疗抵抗性抑郁症、焦虑性抑郁症、躁郁症）、癌症和眼部疾病相关的方法。 其中R1、R2、R2a、R3、R3a、R4和R4a在此处定义。
• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：INFINITY PHARMACEUTICALS, INC.

  公开号：US20130267521A1

  公开（公告）日：2013-10-10

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本发明描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及用于治疗与激酶活性相关的疾病和状况的化合物、药物组合物和方法，包括PI3激酶活性。
• HETEROCYCLIC COMPOUND
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20160159808A1

  公开（公告）日：2016-06-09

  A compound represented by the formula (I): wherein each symbol is as described in the SPECIFICATION, or a salt thereof has a PDE2A inhibitory action, and is useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like.

  化合物的化学式为(I)：其中每个符号如规范中所述，或其盐具有PDE2A抑制作用，并且可用作精神分裂症、阿尔茨海默病等疾病的预防或治疗药物。
• Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate
  作者：Catherine A. Evans、Tao Liu、André Lescarbeau、Somarajan J. Nair、Louis Grenier、Johan A. Pradeilles、Quentin Glenadel、Thomas Tibbitts、Ann M. Rowley、Jonathan P. DiNitto、Erin E. Brophy、Erin L. O’Hearn、Janid A. Ali、David G. Winkler、Stanley I. Goldstein、Patrick O’Hearn、Christian M. Martin、Jennifer G. Hoyt、John R. Soglia、Culver Cheung、Melissa M. Pink、Jennifer L. Proctor、Vito J. Palombella、Martin R. Tremblay、Alfredo C. Castro

  DOI：10.1021/acsmedchemlett.6b00238

  日期：2016.9.8

  Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.

  异喹啉酮PI3K抑制剂的优化导致发现了一种有效的PI3K-γ抑制剂（26或IPI-549），其选择性是其他脂质和蛋白激酶的100倍以上。IPI-549在体内表现出良好的药代动力学特性和对PI3K-γ介导的嗜中性粒细胞迁移的强烈抑制，目前正处于晚期实体瘤患者的1期临床评估中。
• [EN] HETEROCYCLIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS UTILISATIONS
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2013154878A1

  公开（公告）日：2013-10-17

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本文描述了调节激酶活性，包括PI3激酶活性的化合物和制药组合物，以及与激酶活性，包括PI3激酶活性相关的疾病和病症的治疗方法、化合物和制药组合物。