4-[Cyclohexyl-(2-ethoxycarbonyl-ethyl)-amino]-2-methylsulfanyl-pyrimidine-5carboxylic acid ethyl ester | 928640-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-[Cyclohexyl-(2-ethoxycarbonyl-ethyl)-amino]-2-methylsulfanyl-pyrimidine-5carboxylic acid ethyl ester
• 英文别名: 4-[Cyclohexyl-(2-ethoxycarbonyl-ethyl)-amino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester；ethyl 4-[cyclohexyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate
• CAS: 928640-80-6
• 化学式: C₁₉H₂₉N₃O₄S
• 分子量: 395.523
• InChiKey: LUYPTNXKKZDUHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[Cyclohexyl-(2-ethoxycarbonyl-ethyl)-amino]-2-methylsulfanyl-pyrimidine-5carboxylic acid ethyl ester 在 sodium 、 叔丁醇 作用下， 以 甲苯 为溶剂， 反应 0.67h， 以42%的产率得到8-cyclohexyl-2-methylsulfanyl-5-oxo-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester
  参考文献：
  名称：

  5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES AS INHIBITORS OF C-FMS KINASE

  摘要：

  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。

  公开号：

  US20080114007A1
• 作为产物：
  描述：

  4-氯-2-甲硫基嘧啶-5-羧酸乙酯 、 3-(环己基氨基)丙酸乙酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以84%的产率得到4-[Cyclohexyl-(2-ethoxycarbonyl-ethyl)-amino]-2-methylsulfanyl-pyrimidine-5carboxylic acid ethyl ester
  参考文献：
  名称：

  5-Oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase

  摘要：

  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。

  公开号：

  US20070060577A1

文献信息

• 5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase
  申请人：Janssen Pharmaceutica N.V.

  公开号：US07728003B2

  公开（公告）日：2010-06-01

  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, n, Z, and R102 are described in the specification.

  该发明解决了当前对选择性和强效蛋白酪氨酸激酶抑制剂的需求，提供了c-fms激酶的强效抑制剂。该发明涉及式I的新化合物： 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、n、Z和R102在说明书中描述。
• 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。
• 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.
• 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.
• US7642270B2
  申请人：——

  公开号：US7642270B2

  公开（公告）日：2010-01-05