2-[4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide | 1023275-20-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide
• 英文别名: 2-{[4-(3,3-difluoro-1-methylpiperidin-4-yl)phenyl]amino}-8-(2,3-dihydro-1H-inden-5-yl)-N-methoxy-5-oxo-5H,8H-pyrido[2,3-d]pyrimidine-6-carboxamide；2-[4-(3,3-difluoro-1-methylpiperidin-4-yl)anilino]-8-(2,3-dihydro-1H-inden-5-yl)-N-methoxy-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide
• CAS: 1023275-20-8
• 化学式: C₃₀H₃₀F₂N₆O₃
• 分子量: 560.603
• InChiKey: QZCQOYQWDNEOJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.7
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  8-indan-5-yl-2-methylsulfonyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide 、 4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamine 在 溶剂黄146 作用下， 以58%的产率得到2-[4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide
  参考文献：
  名称：

  Pyrido[2,3-d]pyrimidin-5-ones: A Novel Class of Antiinflammatory Macrophage Colony-Stimulating Factor-1 Receptor Inhibitors

  摘要：

  A series of pyrido[2,3-d]pyrimidin-5-ones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). FMS inhibitors may be useful in treating rheumatoid arthritis and other chronic inflammatory diseases. Structure-based optimization of the lead amide analogue 10 led to hydroxamate analogue 37, which possessed excellent potency and an improved pharmacokinetic profile. During the chronic phase of streptococcal cell wall-induced arthritis in rats, compound 37 (10, 3, and 1 mg/kg) was highly effective at reversing established joint swelling. In an adjuvant-induced arthritis model in rats, 37 prevented joint swelling partially at 10 mg/kg. In this model, osteoclastogenesis and bone erosion were prevented by low doses (1 or 0.33 mg/kg) that had minimal impact on inflammation. These data underscore the potential of FMS inhibitors to prevent erosions and reduce symptoms in rheumatoid arthritis.

  DOI：

  10.1021/jm801406h

文献信息

• 5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES AS INHIBITORS OF C-FMS KINASE
  申请人：Player R. Mark

  公开号：US20080114007A1

  公开（公告）日：2008-05-15

  The invention addresses the current need for selective and potent protein tyrosine kinase inhibitors by providing potent inhibitors of c-fms kinase. The invention is directed to the novel compounds of Formula I: or a salt, stereoisomer, tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester, prodrug or metabolite form thereof, wherein A, Y, Z, R 101 and R 200 are described in the specification.

  本发明针对当前对选择性和强效蛋白酪氨酸激酶抑制剂的需求，提供对c-fms激酶的强效抑制剂。本发明涉及以下式I的新化合物： 或其盐、对映体、互变异构体、结晶、多晶型、无定形、溶剂化物、水合物、酯、前药或代谢物形式，其中A、Y、Z、R 101 和R 200 在说明书中有描述。
• [EN] 5-OXO-5,8 - DIHYDRO - PYRIDO - PYRIMIDINES AS INHIBITORS OF C-FMS KINASE<br/>[FR] 5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES COMME INHIBITEURS DE LA KINASE C-FMS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2008055013A2

  公开（公告）日：2008-05-08

  [EN] The invention addresses the current need for selective and potent protein tyrosine kinase inhibitors by providing potent inhibitors of c-fms kinase. The invention is directed to the novel compounds of Formula I: or a salt, stereoisomer, tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester, prodrug or metabolite form thereof, wherein A, Y, Z, R¹⁰¹ and R²⁰⁰ are described in the specification.
  [FR] L'invention traite du besoin actuel en inhibiteurs sélectifs et puissants de protéine tyrosine kinase en proposant des inhibiteurs puissants de la kinase c-fms. L'invention porte sur les nouveaux composés représentés par la Formule I : ou un sel, un stéréoisomère, un tautomère, un dérivé cristallin, un dérivé polymorphe, un dérivé amorphe, un solvate, un hydrate, un ester, un promédicament ou une forme métabolite de celui-ci, et où A, Y, Z, R¹⁰¹ et R²⁰⁰ sont décrits dans la revendication.
• Pyrido[2,3-<i>d</i>]pyrimidin-5-ones: A Novel Class of Antiinflammatory Macrophage Colony-Stimulating Factor-1 Receptor Inhibitors
  作者：Hui Huang、Daniel A. Hutta、James M. Rinker、Huaping Hu、William H. Parsons、Carsten Schubert、Renee L. DesJarlais、Carl S. Crysler、Margery A. Chaikin、Robert R. Donatelli、Yanmin Chen、Deping Cheng、Zhao Zhou、Edward Yurkow、Carl L. Manthey、Mark R. Player

  DOI：10.1021/jm801406h

  日期：2009.2.26

  A series of pyrido[2,3-d]pyrimidin-5-ones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). FMS inhibitors may be useful in treating rheumatoid arthritis and other chronic inflammatory diseases. Structure-based optimization of the lead amide analogue 10 led to hydroxamate analogue 37, which possessed excellent potency and an improved pharmacokinetic profile. During the chronic phase of streptococcal cell wall-induced arthritis in rats, compound 37 (10, 3, and 1 mg/kg) was highly effective at reversing established joint swelling. In an adjuvant-induced arthritis model in rats, 37 prevented joint swelling partially at 10 mg/kg. In this model, osteoclastogenesis and bone erosion were prevented by low doses (1 or 0.33 mg/kg) that had minimal impact on inflammation. These data underscore the potential of FMS inhibitors to prevent erosions and reduce symptoms in rheumatoid arthritis.