8-indan-5-yl-2-{4-[2-(4-methylpiperazin-1-yl)-ethyl]phenylamino}-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester | 928788-76-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 8-indan-5-yl-2-{4-[2-(4-methylpiperazin-1-yl)-ethyl]phenylamino}-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester
• 英文别名: 8-Indan-5-yl-2-{4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester；ethyl 8-(2,3-dihydro-1H-inden-5-yl)-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate
• CAS: 928788-76-5
• 化学式: C₃₂H₃₆N₆O₃
• 分子量: 552.676
• InChiKey: SJIWMSFEFGFDBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  8-indan-5-yl-2-{4-[2-(4-methylpiperazin-1-yl)-ethyl]phenylamino}-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 在 氨 作用下， 以 甲醇 为溶剂， 生成 8-indan-5-yl-2-{4-[2-(4-methylpiperazin-1-yl)-ethyl]phenylamino}-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid amide
  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
• 作为产物：
  描述：

  4-[2-(4-甲基-哌嗪-1-基)-乙基]-苯胺 、 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 以 异丙醇 为溶剂， 生成 8-indan-5-yl-2-{4-[2-(4-methylpiperazin-1-yl)-ethyl]phenylamino}-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester
  参考文献：
  名称：

  Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors

  摘要：

  A series of pyrimidinopyridones has been designed, synthesized and shown to be potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an amide substituent at the 6-position of the pyridone core resulted in a significant potency increase. Compound 24 effectively inhibited in vivo LPS-induced TNF in mice greater than 80%. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.070

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：US20070060577A1

  公开（公告）日：2007-03-15

  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 solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof, wherein: W, A, Y, Z, R 101 and R 200 are described in the specification.

  该发明通过提供c-fms激酶的有效抑制剂来解决当前对选择性和强效蛋白酪氨酸激酶抑制剂的需求。该发明涉及公式I的新化合物：或其溶剂化合物、水合物、互变异构体或药用可接受的盐，其中：W、A、Y、Z、R101和R200如规范中所述。
• 5-oxo-5,8-dihydro-pyrido-pyrimidine as inhibitors of c-fms kinase
  申请人：Janssen Pharmaceutica N.V.

  公开号：US07642270B2

  公开（公告）日：2010-01-05

  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 solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof, wherein: W, A, Y, Z, R101 and R200 are described in the specification.

  本发明旨在提供c-fms激酶的有效抑制剂，以满足当前选择性和强效蛋白酪氨酸激酶抑制剂的需求。本发明涉及公式I的新型化合物：或其溶剂化物、水合物、互变异构体或药学上可接受的盐，其中：W、A、Y、Z、R101和R200在说明书中描述。
• Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors
  作者：Hui Huang、Daniel A. Hutta、Huaping Hu、Renee L. DesJarlais、Carsten Schubert、Ioanna P. Petrounia、Margery A. Chaikin、Carl L. Manthey、Mark R. Player

  DOI：10.1016/j.bmcl.2008.02.070

  日期：2008.4

  A series of pyrimidinopyridones has been designed, synthesized and shown to be potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an amide substituent at the 6-position of the pyridone core resulted in a significant potency increase. Compound 24 effectively inhibited in vivo LPS-induced TNF in mice greater than 80%. (C) 2008 Elsevier Ltd. All rights reserved.
• 5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES AS INHIBITORS OF C-FMS KINASE
  申请人：Janssen Pharmaceutica NV

  公开号：EP1937681A1

  公开（公告）日：2008-07-02
• US7642270B2
  申请人：——

  公开号：US7642270B2

  公开（公告）日：2010-01-05