2-[4-(Trifluoromethyl)phenyl]-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine | 452342-38-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[4-(Trifluoromethyl)phenyl]-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine
• 英文别名: 4-(5-pyridin-2-yl-1H-pyrazol-4-yl)-2-[4-(trifluoromethyl)phenyl]pyridine
• CAS: 452342-38-0
• 化学式: C₂₀H₁₃F₃N₄
• 分子量: 366.345
• InChiKey: JUJSXTHOUVCQGB-UHFFFAOYSA-N

物化性质

• 沸点：
  494.6±45.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-{2-[4-(三氟甲基)苯基]吡啶-4-基}-1-(吡啶-2-基)乙酮 在 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 2-[4-(Trifluoromethyl)phenyl]-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine
  参考文献：
  名称：

  Discovery of 4-{4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388):  A Potent, Selective, and Orally Active Transforming Growth Factor-β Type I Receptor Inhibitor

  摘要：

  Inhibitors of transforming, growth factor beta (TGF-beta) type I receptor (ALK5) offer a novel approach for the treatment of fibrotic diseases Such as renal, hepatic, and pulmonary fibrosis. The optimization of a novel phenylpyridine pyrazole series (1a) led to the identification of potent, selective, and orally active ALK5 inhibitors. The cellular potency and pharmacokinetics profiles of these derivatives were improved and several compounds presented antifibrotic activity when orally administered to rats in an acute liver model of dimethylnitrosamine- (DMN-) induced expression of collagen IA1 mRNA, a major gene contributing to excessive extra cellular matrix deposit. One of the most potent ALK5 inhibitors identified in this chemical series, Compound 13d (GW788388), reduced the expression of collagen IA1 by 80% at a dose of I mg/kg, twice a day (b.i.d.). This compound significantly reduced the expression of collagen IAI mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis.

  DOI：

  10.1021/jm0509905

文献信息

• ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES
  申请人：Synthis, LLC

  公开号：US20200147234A1

  公开（公告）日：2020-05-14

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

  本公开涉及包含ALK5抑制剂的抗体药物偶联物及其用途。
• [EN] PYRAZOLE DERIVATIVES AGAINST TGF OVEREXPRESSION<br/>[FR] DERIVES PYRAZOLE CONTRE LA SUREXPRESSION DU FACTEUR
  申请人：GLAXO GROUP LTD

  公开号：WO2002066462A1

  公开（公告）日：2002-08-29

  Therapeutically active pyrazole derivatives of formula (I) wherein R1-R3 are as defined in the specification, processes for the preparation thereof, the use thereof in therapy, particularly in the treatment or prophylaxis of disorders characterised by overexpression of transforming growth factor β (TGF-β), and pharmaceutical compositions for use in such therapy. Formula (I)

  公式（I）中的治疗活性吡唑衍生物，其中R1-R3如规范中所定义，其制备过程，其在治疗中的使用，特别是在治疗或预防表现为过度表达转化生长因子β（TGF-β）的疾病中的使用，以及用于这种治疗的制药组合物。 公式（I）
• Pyrazole derivatives against tgf overexpression
  申请人：——

  公开号：US20040087623A1

  公开（公告）日：2004-05-06

  Therapeutically active pyrazole derivatives of formula (I) wherein R 1 -R 3 are as defined in the specification, processes for the preparation thereof, the use thereof in therapy, particularly in the treatment or prophylaxis of disorders characterised by overexpression of transforming growth factor &bgr; (TGF-&bgr;), and pharmaceutical compositions for use in such therapy, Formula (I) 1

  公式（I）中的治疗活性吡唑衍生物，其中R1-R3如规范中所定义，其制备过程，其在治疗中的使用，特别是在治疗或预防表现为转化生长因子&bgr;（TGF-&bgr;）过度表达的疾病中的使用，以及用于此类治疗的制药组合物，公式（I）1
• Compounds and methods for selectively targeting tumor-associated mucins
  申请人：B & G Partners, LLC

  公开号：EP2409708A1

  公开（公告）日：2012-01-25

  The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

  本发明涉及含有肿瘤选择性靶向抑制剂糖共轭物的药物组合物。这些生物共轭物是与生物相容性载体分子共价结合的 ALK5 抑制剂，可选择性地靶向和特异性地结合多种肿瘤细胞类型上过度表达的 Muc4。ALK5 抑制剂通过共价连接体与肿瘤靶向性聚糖共轭。最好设计成在血浆中稳定，并在靶向肿瘤的酸性环境中通过酸催化水解释放出具有药理活性的抑制剂，从而恢复抑制剂的活性。由于糖轭合物在生理pH值和血浆中稳定，因此它们能减少不希望出现的全身性ALK5抑制剂活性；然而，优选的糖轭合物是耐酸轭合物，在到达肿瘤的酸性环境时可被水解。
• PYRAZOLE DERIVATIVES AGAINST TGF OVEREXPRESSION
  申请人：SmithKline Beecham Corporation

  公开号：EP1355903B1

  公开（公告）日：2005-03-16