[2,3'-Bipyridine]-4-carboxylic acid | 1214384-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [2,3'-Bipyridine]-4-carboxylic acid
• 英文别名: 2-pyridin-3-ylpyridine-4-carboxylic acid
• CAS: 1214384-41-4
• 化学式: C₁₁H₈N₂O₂
• 分子量: 200.197
• InChiKey: ZGPKFTUSQWWSDH-UHFFFAOYSA-N

物化性质

• 沸点：
  515.9±40.0 °C(Predicted)
• 密度：
  1.302±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 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：

  [2,3'-Bipyridine]-4-carboxylic acid 、 1-(2-amino-1H-benzo[d]imidazol-1-yl)-2-methylpropan-2-ol 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 [2,3′]bipyridinyl-4-carboxylic acid [1-(2-hydroxy-2-methyl-propyl)-1H-benzoimidazol-2-yl]-amide
  参考文献：
  名称：

  Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

  摘要：

  The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macro-cyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFR(del19 T790M C797S) xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

  DOI：

  10.1021/acs.jmedchem.9b01169
• 作为产物：
  描述：

  2-溴吡啶-4-甲酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 18.0h， 生成 [2,3'-Bipyridine]-4-carboxylic acid
  参考文献：
  名称：

  Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

  摘要：

  The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macro-cyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFR(del19 T790M C797S) xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

  DOI：

  10.1021/acs.jmedchem.9b01169

文献信息

• [EN] NEW BENZIMIDAZOLE COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS DE BENZIMIDAZOLE ET LEURS DÉRIVÉS EN TANT QU'INHIBITEURS D'EGFR
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2019162323A1

  公开（公告）日：2019-08-29

  The present invention encompasses compounds of formula (I) (I), wherein the groups R1 to R5 have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

  本发明涵盖了式（I）（I）的化合物，其中基团R1至R5具有权利要求和说明书中给出的含义，它们作为突变EGFR的抑制剂的用途，含有这种化合物的药物组合物以及它们作为药物/医用品的用途，特别是作为治疗和/或预防肿瘤疾病的药剂。
• [EN] PYRIDINESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF<br/>[FR] DÉRIVATIFS DE PYRIDINESULFONAMIDE POUVANT ÊTRE UTILISÉS COMME MODULATEURS TRAP1 ET LEURS UTILISATIONS
  申请人：AMATHUS THERAPEUTICS INC

  公开号：WO2021188907A1

  公开（公告）日：2021-09-23

  The present disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor ("TNF") receptor associated protein 1 ("TRAP1") modulators (e.g., TRAP1 activators). The provided compounds may also rescue the activity in PTEN-induced kinase 1 ("PINK1") loss of function contexts. The provided compounds may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds may also refold or solubilize aggregated or misfolded proteins such as a-synuclein. The present disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof).

  本公开提供了化合物的化学式（I）和药学上可接受的盐、溶剂化合物、水合物、多晶型、共晶体、互变异构体、立体异构体、同位素标记化合物以及其前药。所提供的化合物可能是肿瘤坏死因子（"TNF"）受体相关蛋白1（"TRAP1"）调节剂（例如，TRAP1激活剂）。所提供的化合物还可能恢复PTEN诱导的激酶1（"PINK1"）功能丧失情况下的活性。所提供的化合物还可能改善线粒体的健康、功能、质量、数量和/或活性，和/或减少活性氧自由基的产生。所提供的化合物还可能对聚集或错误折叠的蛋白质（如α-突触核蛋白）进行重折叠或溶解。本公开还提供了包括所提供化合物的药物组合物；包括所提供化合物或药物组合物的试剂盒；以及使用所提供的化合物和药物组合物的方法（例如，用于治疗需要的受试者的疾病）。
• [EN] COMBINATION OF MGLUR2 ANTAGONIST AND ACHE INHIBITOR FOR TREATMENT OF ACUTE AND/OR CHRONIC NEUROLOGICAL DISORDERS<br/>[FR] COMBINAISON D'ANTAGONISTE MGLUR2 ET D'INHIBITEUR ACHE DESTINEE AU TRAITEMENT DE TROUBLES NEUROLOGIQUES AIGUS ET/OU CHRONIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005014002A1

  公开（公告）日：2005-02-17

  The present invention relates to a method of treatment or prevention of acute and/or chronic neurological disorders, to a pharmaceutical composition comprising an inhibitor of acetylcholinesterase (AChE inhibitor) and a metabotropic Glutamate receptor 2 antagonist (mGluR2 antagonist), to the use of an AChE inhibitor and a mGluR2 antagonist in the preparation of a medicament, and. to kits comprising an AChE inhibitor and a mGluR2 antagonist.

  本发明涉及一种治疗或预防急性和/或慢性神经系统疾病的方法，涉及一种包含乙酰胆碱酯酶抑制剂（AChE抑制剂）和代谢型谷氨酸受体2拮抗剂（mGluR2拮抗剂）的药物组合物，涉及在制备药物中使用AChE抑制剂和mGluR2拮抗剂，以及包含AChE抑制剂和mGluR2拮抗剂的试剂盒。
• Substituted pyrazole compounds useful as soluble epoxide hyrolase inhibitors
  申请人：Fleck Roman Wolfgang

  公开号：US20090227588A1

  公开（公告）日：2009-09-10

  Disclosed are compounds active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same.

  本发明涉及对可溶性环氧水解酶（sEH）活性的化合物，其组成物和使用和制备它们的方法。
• Benzimidazole compounds and derivatives as EGFR inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US11174245B2

  公开（公告）日：2021-11-16

  The present invention encompasses compounds of formula (I) (I), wherein the groups R1 to R5 have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

  本发明包括式(I)(I)化合物（其中基团R1至R5具有权利要求书和说明书中给出的含义）、它们作为突变型表皮生长因子受体抑制剂的用途、含有此类化合物的药物组合物以及它们作为药物/医疗用途的用途，特别是作为治疗和/或预防肿瘤疾病的制剂的用途。