(4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)phenyl)methanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)phenyl)methanol
• 英文别名: [4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)-phenyl]-methanol；[4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]phenyl]methanol
• 化学式: C₂₂H₁₇N₃O₃
• 分子量: 371.395
• InChiKey: OXDOLEPGFYPERU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 4-[4-(3,4-methylenedioxyphenyl)-5-(2-pyridyl)-1H-imidazol-2-yl]benzoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以54%的产率得到(4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)phenyl)methanol
  参考文献：
  名称：

  Identification of Novel Inhibitors of the Transforming Growth Factor β1 (TGF-β1) Type 1 Receptor (ALK5)

  摘要：

  Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.

  DOI：

  10.1021/jm010493y

文献信息

• 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。
• ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES
  申请人：Synthis Therapeutics, Inc.

  公开号：US20220249680A1

  公开（公告）日：2022-08-11

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.
• US8871744B2
  申请人：——

  公开号：US8871744B2

  公开（公告）日：2014-10-28
• Identification of Novel Inhibitors of the Transforming Growth Factor β1 (TGF-β1) Type 1 Receptor (ALK5)
  作者：James F. Callahan、Joelle L. Burgess、James A. Fornwald、Laramie M. Gaster、John D. Harling、Frank P. Harrington、Jag Heer、Chet Kwon、Ruth Lehr、A. Mathur、Barbara A. Olson、Joseph Weinstock、Nicholas J. Laping

  DOI：10.1021/jm010493y

  日期：2002.2.1

  Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.