ethyl 6-(2'-formylbiphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate | 543744-69-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 6-(2'-formylbiphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate
• 英文别名: 6-(2'-formyl-biphenyl-4-yl)-1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester；ethyl 6-(2'-formyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate；ethyl 6-[4-(2-formylphenyl)phenyl]-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxylate
• CAS: 543744-69-0
• 化学式: C₂₉H₂₅N₃O₅
• 分子量: 495.535
• InChiKey: AELDDWZBSAWWAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  90.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-(2'-formylbiphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate 在 氯化锌 盐酸甲胺 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到1-(4-Methoxy-phenyl)-6-(2'-methylaminomethyl-biphenyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c)pyridine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Substituted amino methyl factor Xa inhibitors

  摘要：

  本申请描述了替代氨甲基取代化合物及其衍生物，或其药用盐形式，这些化合物可用作因子Xa的抑制剂。

  公开号：

  US20030212054A1
• 作为产物：
  描述：

  6-(4-碘苯基)-1-(4-甲氧基苯基)-7-氧代-4,5,6,7-四氢-1H-吡唑并[3,4-c]吡啶-3-羧酸 、 2-甲酰基苯硼酸 在 Pd(PPh3)4 potassium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 生成 ethyl 6-(2'-formylbiphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis of 4,5-dihydro-pyrazolo [3,4-c] pyrid-2-ones

  摘要：

  描述了一种从适当的苯基肼制备下列类型的4,5-二氢吡唑并[3,4-c]吡啶-2-酮的新型工艺和中间体。这些化合物可用作因子Xa抑制剂。

  公开号：

  US20030181466A1

文献信息

• Synthesis of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones
  申请人：Bristol-Myers Squibb Company

  公开号：US07153960B2

  公开（公告）日：2006-12-26

  A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds are useful as factor Xa inhibitors.

  介绍了一种从适当的苯基肼制备4,5-二氢嘧唑并[3,4-c]吡啶-2-酮的新工艺和中间体。这些化合物可用作因子Xa抑制剂。
• SYNTHESIS OF 4,5-DIHYDRO-PYRAZOLO[3,4-C]PYRID-2-ONES
  申请人：Zhou Jiacheng

  公开号：US20070027186A1

  公开（公告）日：2007-02-01

  A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds are useful as factor Xa inhibitors.

  本文描述了一种从适当的苯基肼制备下列类型的4,5-二氢吡唑并[3,4-c]吡啶-2-酮的新工艺及其中间体。这些化合物可用作因子Xa抑制剂。
• Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1<i>H</i>-pyrazolo[3,4-<i>c</i>]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa
  作者：Donald J. P. Pinto、Michael J. Orwat、Stephanie Koch、Karen A. Rossi、Richard S. Alexander、Angela Smallwood、Pancras C. Wong、Alan R. Rendina、Joseph M. Luettgen、Robert M. Knabb、Kan He、Baomin Xin、Ruth R. Wexler、Patrick Y. S. Lam

  DOI：10.1021/jm070245n

  日期：2007.11.1

  Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P-1 moieties that resulted in the identification of the p-methoxyphenyl P-1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P-4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidinl-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.
• US6884890B2
  申请人：——

  公开号：US6884890B2

  公开（公告）日：2005-04-26
• US6919451B2
  申请人：——

  公开号：US6919451B2

  公开（公告）日：2005-07-19