2-(4-Fluorophenyl)-1-[8-(2-methylsulfanylpyrimidine-4-carbonyl)-1,4-dioxa-7,8-diazaspiro[4.4]nonan-7-yl]ethanone | 503303-80-8

• 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: 2-(4-Fluorophenyl)-1-[8-(2-methylsulfanylpyrimidine-4-carbonyl)-1,4-dioxa-7,8-diazaspiro[4.4]nonan-7-yl]ethanone
• CAS: 503303-80-8
• 化学式: C₁₉H₁₉FN₄O₄S
• 分子量: 418.449
• InChiKey: KBZXTVNNFAURPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4-Fluorophenyl)-1-[8-(2-methylsulfanylpyrimidine-4-carbonyl)-1,4-dioxa-7,8-diazaspiro[4.4]nonan-7-yl]ethanone 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2'-(4-Fluorophenyl)-1'-[2-[(3-methylphenyl)methylamino]pyrimidin-4-yl]spiro[1,3-dioxolane-2,6'-5,7-dihydropyrazolo[1,2-a]pyrazole]-3'-one
  参考文献：
  名称：

  The development of novel inhibitors of tumor necrosis factor-α (TNF-α) production based on substituted [5,5]-bicyclic pyrazolones

  摘要：

  Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-alpha production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.001
• 作为产物：
  描述：

  对氟苯乙酰氯 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 对甲苯磺酸 、 臭氧 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 2-(4-Fluorophenyl)-1-[8-(2-methylsulfanylpyrimidine-4-carbonyl)-1,4-dioxa-7,8-diazaspiro[4.4]nonan-7-yl]ethanone
  参考文献：
  名称：

  The development of novel inhibitors of tumor necrosis factor-α (TNF-α) production based on substituted [5,5]-bicyclic pyrazolones

  摘要：

  Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-alpha production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.001

文献信息

• Convergent synthesis of 2,3-bisarylpyrazolones through cyclization of bisacylated pyrazolidines and hydrazines
  作者：Todd A. Brugel、Tomas Hudlicky、Michael P. Clark、Adam Golebiowski、Mark Sabat、Mary Ann A. Endoma、Vu Bui、David Adams、Matthew J. Laufersweiler、Jennifer A. Maier、Roger G. Bookland、Biswanath De

  DOI：10.1016/j.tetlet.2006.03.063

  日期：2006.5

  Cyclization of various bisacylated hydrazines and pyrazolidines using DBU or sodium hydride leads to the formation of various mono-, bi- and tricyclic pyrazolone scaffolds in 41-98% yield. The convergent nature by which the precyclization intermediates are constructed allows for rapid derivatization about the pyrazolone core. (c) 2006 Elsevier Ltd. All rights reserved.
• The development of novel inhibitors of tumor necrosis factor-α (TNF-α) production based on substituted [5,5]-bicyclic pyrazolones
  作者：Matthew J Laufersweiler、Todd A Brugel、Michael P Clark、Adam Golebiowski、Roger G Bookland、Steven K Laughlin、Mark P Sabat、Jennifer A Townes、John C VanRens、Biswanath De、Lily C Hsieh、Sandra A Heitmeyer、Karen Juergens、Kimberly K Brown、Marlene J Mekel、Richard L Walter、Michael J Janusz

  DOI：10.1016/j.bmcl.2004.06.001

  日期：2004.8

  Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-alpha production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed. (C) 2004 Elsevier Ltd. All rights reserved.