GDC-0879 | 2230954-03-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: GDC-0879
• 英文别名: 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol；(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime；2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol
• CAS: 2230954-03-5
• 化学式: C₁₉H₁₈N₄O₂
• 分子量: 334.378
• InChiKey: DEZZLWQELQORIU-RELWKKBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(1-(2-hydroxyethyl)-3-pyridin-4-yl-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 以78%的产率得到GDC-0879
  参考文献：
  名称：

  Potent and selective pyrazole-based inhibitors of B-Raf kinase

  摘要：

  Herein we describe a novel pyrazole-based class of ATP competitive B-Raf inhibitors. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. A subset of these inhibitors has demonstrated the ability to inhibit downstream ERK phosphorylation in LOX tumors from mouse xenograft studies.

  DOI：

  10.1016/j.bmcl.2008.07.002

文献信息

• [EN] AXL-SPECIFIC ANTIBODY-DRUG CONJUGATES FOR CANCER TREATMENT<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT SPÉCIFIQUES D'AXL POUR LE TRAITEMENT DU CANCER
  申请人：GENMAB AS

  公开号：WO2017009258A1

  公开（公告）日：2017-01-19

  The present disclosure relates to antibody-drug conjugates (ADCs) binding to human AXL for therapeutic use, particularly for treatment of resistant or refractory cancers.

  本公开涉及抗体药物偶联物（ADCs）与人类AXL结合，特别用于治疗耐药或难治性癌症。
• [EN] 6, 7-RING-FUSED TRIAZOLO [4, 3 - B] PYRIDAZINE DERIVATIVES AS PIM INHIBITORS<br/>[FR] DÉRIVÉS DE TRIAZOLO[4,3-B]PYRIDAZINES AU CYCLE 6,7 FUSIONNÉ UTILISÉS EN TANT QU'INHIBITEURS DE PIM
  申请人：CT NAC INVESTIGACIONES ONCOLOGICAS CNIO

  公开号：WO2012098387A1

  公开（公告）日：2012-07-26

  There is provided compounds of formula I, wherein R1, R2, R3 and R4 (and the -CH2-CH2 moiety) have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

  提供了式I的化合物，其中R1、R2、R3和R4（以及-CH2- 基团）的含义如描述中所示，并且其药学上可接受的酯、酰胺、溶剂合物或盐，这些化合物在治疗需要或期望抑制蛋白激酶或脂质激酶（例如PIM家族激酶，如PIM-1、PIM-2和/或PIM-3）的疾病中非常有用，特别是在癌症或增生性疾病的治疗中。
• [EN] FORMYLATED N-HETEROCYCLIC DERIVATIVES AS FGFR4 INHIBITORS<br/>[FR] DÉRIVÉS N-HÉTÉROCYCLIQUES FORMYLÉS UTILISÉS EN TANT QU'INHIBITEURS DE FGFR4
  申请人：NOVARTIS AG

  公开号：WO2016151499A1

  公开（公告）日：2016-09-29

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; (I) a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.

  本发明提供了化合物(I)或其药学上可接受的盐；(I)制造该化合物的方法及其治疗用途。本发明还提供了药理活性剂的组合物和包含该化合物的药物组合物。
• [EN] AMINOPYRIMIDINYLAMINOBENZONITRILE DERIVATIVES AS NEK2 INHIBITORS<br/>[FR] DÉRIVÉS D'AMINOPYRIMIDINYLAMINOBENZONITRILE UTILISÉS EN TANT QU'INHIBITEURS DE NEK2
  申请人：SUMITOMO DAINIPPON PHARMA ONCOLOGY INC

  公开号：WO2021155185A1

  公开（公告）日：2021-08-05

  The present invention provides aminopyrimidinylaminobenzonitrile compounds that inhibit the activity of never in mitosis gene A-related kinase 2 (NEK2) and are useful in the treatment of diseases related to activity of NEK2, including cancer (e.g., multiple myeloma, and breast, liver, pancreatic and colorectal cancers).

  本发明提供了一种氨基嘧啶基氨基苯甲腈化合物，可以抑制与未在有丝分裂基因A相关激酶2（NEK2）的活性相关的疾病的治疗中起作用，包括癌症（例如多发性骨髓瘤、乳腺癌、肝癌、胰腺癌和结直肠癌）。
• [EN] HETERO-BIFUNCTIONAL DEGRADER COMPOUNDS AND THEIR USE AS MODULATORS OF TARGETED UBIQUINATION (VHL)<br/>[FR] COMPOSÉS DE DÉGRADATION HÉTÉRO-BIFONCTIONNELS ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'UBIQUINATION CIBLÉE (VHL)
  申请人：GENENTECH INC

  公开号：WO2019183523A1

  公开（公告）日：2019-09-26

  The present disclosure relates to bifunctional compounds, which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds that contain on one end a VHL ligand moiety, which binds to the VHL ubiquitin ligase (E3), and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. The target protein may be EGFR. Also disclosed are VHL ligands.

  本公开涉及双功能化合物，可用作靶向泛素化的调节剂。特别是，本公开是针对包含在一端具有VHL配体基团的化合物，该基团结合到VHL泛素连接酶(E3)，而在另一端具有结合目标蛋白的基团，从而实现目标蛋白/多肽的降解。目标蛋白可以是EGFR。还公开了VHL配体。