2-(2-溴吡啶-4-基)-1-(吡啶-2-基)乙酮 | 446852-65-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(2-溴吡啶-4-基)-1-(吡啶-2-基)乙酮
• 英文名称: 2-(2-bromopyridin-4-yl)-1-(pyridin-2-yl)ethan-1-one
• 英文别名: 2-(2-Bromopyridin-4-yl)-1-(pyridin-2-yl)ethanone；2-(2-bromopyridin-4-yl)-1-pyridin-2-ylethanone
• CAS: 446852-65-9
• 化学式: C₁₂H₉BrN₂O
• 分子量: 277.12
• InChiKey: RKVGSLYSLROWJI-UHFFFAOYSA-N

物化性质

• 沸点：
  420.4±35.0 °C(Predicted)
• 密度：
  1.503±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-(2-溴吡啶-4-基)-1-(吡啶-2-基)乙酮 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 29.3h， 生成 2-(4-hydroxyphenyl)-4-(3-pyridin-2-yl-1-trityl-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
• 作为产物：
  描述：

  2-溴-4-甲基吡啶 、 2-吡啶甲酸乙酯 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 2-(2-溴吡啶-4-基)-1-(吡啶-2-基)乙酮
  参考文献：
  名称：

  [EN] 2-PHENYLPYRIDIN-4-YL DERIVATIVES AS ALK5 INHIBITORS
  [FR] DERIVES DE C2-PHENYLPYRIDINE-4-YL EN TANT QU'INHIBITEURS D'ALK5

  摘要：

  本发明涉及一类新颖的2-苯基吡啶-4-基杂环衍生物，这些衍生物是转化生长因子('TGF')-β信号通路的抑制剂，特别是TGF-β I型或激活素样激酶('ALK')-5受体介导的smad2或smad3磷酸化的抑制剂，以及这些衍生物的制备方法和在医学上的应用，特别是在治疗和预防由该通路介导的疾病状态方面的应用。

  公开号：

  WO2004013135A1

文献信息

• Formulated and/or co-formulated liposome compositions containing TFGB antagonist prodrugs useful in the treatment of cancer and methods thereof
  申请人：Nammi Therapeutics, Inc.

  公开号：US20210260197A1

  公开（公告）日：2021-08-26

  Formulated and/or co-formulated liposomes (LNP) and solid-lipid nanoparticles (SLNP) comprising TB Prodrugs and methods of making the LNPs and SLNPs are disclosed herein. The TB prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit ALK5. The TB Prodrugs can be formulated and/or co-formulated into a liposome or solid-lipid nanoparticle to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

  本文揭示了制备和/或共同制备的脂质体（LNP）和固体脂质纳米粒子（SLNP），其中包括TB前药，并公开了制备LNP和SLNP的方法。TB前药组合物包括药物基团、脂质基团和抑制ALK5的连接单元。TB前药可以配制和/或共同配制成脂质体或固体脂质纳米粒子，以提供一种治疗癌症、免疫性疾病和其他疾病的方法，利用靶向药物传递载体。
• [EN] ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES<br/>[FR] CONJUGUÉS D'ANTICORPS-INHIBITEUR ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS LLC

  公开号：WO2020013803A1

  公开（公告）日：2020-01-16

  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。
• 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] ANTIB0DY-ALK5 INHIBITOR CONJUGATES AND THEIR USES<br/>[FR] CONJUGUÉS D'ANTICORPS-INHIBITEUR DE ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS LLC

  公开号：WO2020256751A1

  公开（公告）日：2020-12-24

  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] ALK5 INHIBITOR CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS INHIBITEURS D'ALK5 ET LEURS UTILISATIONS
  申请人：SYNTHIS THERAPEUTICS INC

  公开号：WO2021142086A1

  公开（公告）日：2021-07-15

  The present disclosure relates to targeted drug conjugates comprising ALK5 inhibitors and targeting moieties that direct the ALK5 inhibitors to cells involved in fibrosis and cancer, for example myofibroblasts, activated fibroblasts and transitioning fibroblasts, and their uses, in particular wherein the ALK5 inhibitor is N-methyl-2-(4-(4-(3-(6- methylpyridin-2-yl)-l H-pyrazol-4-yl)pyridin-2-yl)phenoxy)ethan-l- amine.

  本公开涉及包含ALK5抑制剂和靶向基团的靶向药物结合物，该靶向基团将ALK5抑制剂定向到参与纤维化和癌症的细胞，例如肌成纤维细胞、活化成纤维细胞和转变成纤维细胞，以及它们的用途，特别是其中ALK5抑制剂是N-甲基-2-(4-(4-(3-(6-甲基吡啶-2-基)-1H-吡唑-4-基)吡啶-2-基)苯氧基)乙基-1-胺。