4-[4-(3-pyridin-2-yl-1-trityl-1H-pyrazol-4-yl)pyridin-2-yl]benzoic acid | 452343-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-[4-(3-pyridin-2-yl-1-trityl-1H-pyrazol-4-yl)pyridin-2-yl]benzoic acid
• 英文别名: 4-(4-(3-(pyridin-2-yl)-1-trityl-1H-pyrazol-4-yl)pyridin-2-yl)benzoic acid；4-[4-(3-pyridin-2-yl-1-tritylpyrazol-4-yl)pyridin-2-yl]benzoic acid
• CAS: 452343-18-9
• 化学式: C₃₉H₂₈N₄O₂
• 分子量: 584.677
• InChiKey: YDGLZJRYPWVPEH-UHFFFAOYSA-N

物化性质

• 沸点：
  765.1±60.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(3-pyridin-2-yl-1-trityl-1H-pyrazol-4-yl)pyridin-2-yl]benzoic acid 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-Methyl-4-[4-(3-pyridin-2-yl-1H-pyrazol-4-yl)-pyridin-2-yl]-N-(tetrahydro-pyran-4-yl)-benzamide
  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-吡啶甲酸乙酯 在 sodium hydroxide 、 四(三苯基膦)钯 、 双(三甲基硅烷基)氨基钾 、 sodium carbonate 、 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 47.8h， 生成 4-[4-(3-pyridin-2-yl-1-trityl-1H-pyrazol-4-yl)pyridin-2-yl]benzoic acid
  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

• 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。
• 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
• PYRAZOLE DERIVATIVES AGAINST TGF OVEREXPRESSION
  申请人：SmithKline Beecham Corporation

  公开号：EP1355903B1

  公开（公告）日：2005-03-16
• Discovery of 4-{4-[3-(Pyridin-2-yl)-1<i>H</i>-pyrazol-4-yl]pyridin-2-yl}-<i>N</i>-(tetrahydro-2<i>H</i>- pyran-4-yl)benzamide (GW788388):  A Potent, Selective, and Orally Active Transforming Growth Factor-β Type I Receptor Inhibitor
  作者：Françoise Gellibert、Anne-Charlotte de Gouville、James Woolven、Neil Mathews、Van-Loc Nguyen、Cécile Bertho-Ruault、Angela Patikis、Eugene T. Grygielko、Nicholas J. Laping、Stéphane Huet

  DOI：10.1021/jm0509905

  日期：2006.4.1

  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.