4-[5-methyl-3-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-[5-methyl-3-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-quinoline
• 英文别名: 4-[5-Methyl-3-(6-methyl-pyridin-2-yl)-1H-pyrazol-4-yl]-quinoline；4-[5-methyl-3-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]quinoline
• 化学式: C₁₉H₁₆N₄
• 分子量: 300.363
• InChiKey: AMZUNRUJZDTWPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-甲基-2-吡啶甲酸甲酯 在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 36.42h， 生成 4-[5-methyl-3-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-quinoline
  参考文献：
  名称：

  Synthesis and Activity of New Aryl- and Heteroaryl-Substituted Pyrazole Inhibitors of the Transforming Growth Factor-β Type I Receptor Kinase Domain

  摘要：

  Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAP, in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.

  DOI：

  10.1021/jm0205705

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。
• CONTROL OF INTRAOCULAR PRESSURE USING ALK5 MODULATION AGENTS
  申请人：Fleenor Debra L.

  公开号：US20120115870A1

  公开（公告）日：2012-05-10

  An ophthalmic pharmaceutical composition useful in the treatment of glaucoma and control of intraocular pressure comprising an effective amount of a selective modulator of ALK5 receptor activity is disclosed. Also disclosed is a method of treating glaucoma and controlling intraocular pressure comprising applying a therapeutically effective amount of a pharmaceutical composition comprising a selective modulator of ALK5 receptor activity to an affected eye of a patient.

  本发明公开了一种眼科制药组合物，可用于治疗青光眼和控制眼压，包括一种有效量的ALK5受体活性选择性调节剂。本发明还公开了一种治疗青光眼和控制眼压的方法，包括向患者受影响的眼睛中施用含有ALK5受体活性选择性调节剂的治疗有效量的药物组合物。
• 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。
• US8871744B2
  申请人：——

  公开号：US8871744B2

  公开（公告）日：2014-10-28
• [EN] METHODS OF INHIBITING TGF BETA WITH SUBSTITUTED PYRAZOLES<br/>[FR] PROCEDES RELATIFS A L'INHIBITION DU TGF-BETA PAR LE BIAIS DE PYRAZOLES SUBSTITUES
  申请人：LILLY CO ELI

  公开号：WO2004026302A1

  公开（公告）日：2004-04-01

  Substituted pyrazoles are disclosed useful in the treatment of cancer and other disease states influenced by TGF beta by inhibiting TGF-β in a patient in need thereof.