4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-trifluoromethoxy-quinoline | 476474-62-1

• 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-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-trifluoromethoxy-quinoline
• 英文别名: 4-[2-(6-Methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-trifluoromethoxyquinolin；Dihydropyrrolopyrazole, 7f；4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-(trifluoromethoxy)quinoline
• CAS: 476474-62-1
• 化学式: C₂₂H₁₇F₃N₄O
• 分子量: 410.398
• InChiKey: SRIWDROQQPUKBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(1-(6-methylpyridin-2-yl)-2-(6-(trifluoromethoxy)quinolin-4-yl)ethylideneamino)pyrrolidin-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-trifluoromethoxy-quinoline
  参考文献：
  名称：

  Optimization of a Dihydropyrrolopyrazole Series of Transforming Growth Factor-β Type I Receptor Kinase Domain Inhibitors: Discovery of an Orally Bioavailable Transforming Growth Factor-β Receptor Type I Inhibitor as Antitumor Agent

  摘要：

  In our continuing effort to expand the SAR of the quinoline domain of dihydropyrrolopyrazole series, we have discovered compound 15d, which demonstrated the antitumor efficacy with oral bioavailability. This effort also demonstrated that the PK/PD in vivo target inhibition paradigm is an effective approach to assess potential for antitumor efficacy. The dihydropyrrolopyrazole inhibitor 15d (LY2109761) is representative of a novel series of antitumor agents.

  DOI：

  10.1021/jm701199p

文献信息

• [EN] NOVEL PYRROLE DERIVATIVES AS PHARMACEUTICAL AGENTS<br/>[FR] DERIVES DE PYRROLE UTILISES COMME AGENTS PHARMACEUTIQUES
  申请人：LILLY CO ELI

  公开号：WO2002094833A1

  公开（公告）日：2002-11-28

  Novel pyrrazole derivative compounds and their use as pharmaceutical agents, in particular their use as TGF-beta signal transduction inhibitors. The disclosed invention relates to compounds of the structure (I) wherein (I) is a four, five, or six membered saturated ring and X is C, O or S.

  小说吡唑衍生物化合物及其作为药物制剂的用途，特别是作为TGF-beta信号传导抑制剂的用途。所披露的发明涉及结构为（I）的化合物，其中（I）是四、五或六元饱和环，X为C，O或S。
• Novel pyrrole derivatives as pharmaceutical agents
  申请人：——

  公开号：US20040106604A1

  公开（公告）日：2004-06-03

  Novel pyrrazole derivative compounds and their use as pharmaceutical agents, in particular their use as TGF-beta signal transduction inhibitors. The disclosed invention relates to compounds of the structure (I) wherein (I) is a four, five, or six membered saturated ring and X is C, O or S. 1

  小说吡唑衍生物化合物及其作为药物代理的使用，特别是其作为TGF-beta信号转导抑制剂的使用。所公开的发明涉及结构（I）的化合物，其中（I）是四、五或六个成员的饱和环，X是C、O或S。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。
• NOVEL PYRROLE DERIVATIVES AS PHARMACEUTICAL AGENTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1397364A1

  公开（公告）日：2004-03-17
• EFFICIENT INDUCTION OF PLURIPOTENT STEM CELLS USING SMALL MOLECULE COMPOUNDS
  申请人：Ichida Justin

  公开号：US20120021519A1

  公开（公告）日：2012-01-26

  The disclosure features a method of producing a reprogrammed cell (e.g. an induced pluripotent stem cell or an undifferentiated cell) from a differentiated (e.g. somatic) cell. In some embodiments, the methods includes contacting a differentiated (e.g. somatic cell) with a TGFBR1 inhibitor or anti-TGF-β-antibody to produce a reprogrammed cell (e.g. pluripotent stem cell or undifferentiated cell). Embodiments of the present invention relate to a reprogrammed cell and methods and compositions for producing a chemically produced reprogrammed cell or populations thereof.