1-(4-Fluorophenyl)-1-[2-(propan-2-ylamino)pyrimidin-4-yl]-3-(pyridin-2-ylmethyl)urea | 898799-73-0

• 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: 1-(4-Fluorophenyl)-1-[2-(propan-2-ylamino)pyrimidin-4-yl]-3-(pyridin-2-ylmethyl)urea
• CAS: 898799-73-0
• 化学式: C₂₀H₂₁FN₆O
• 分子量: 380.425
• InChiKey: RPOUNKVBTKDMCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨甲基吡啶 、 (4-Fluorophenyl)-(2-isopropylamino-pyrimidin-4-yl)-carbamic acid 4-nitro-phenyl ester 以 二氯甲烷 为溶剂， 生成 1-(4-Fluorophenyl)-1-[2-(propan-2-ylamino)pyrimidin-4-yl]-3-(pyridin-2-ylmethyl)urea
  参考文献：
  名称：

  N-2,4-嘧啶-N-苯基-N'-烷基脲作为肿瘤坏死因子α（TNF-α）合成的口服活性抑制剂的开发。第2部分。

  摘要：

  描述了一种基于N-2，4-嘧啶-N-苯基-N'-烷基脲支架的新型肿瘤坏死因子α（TNF-α）合成抑制剂。这些化合物中有许多对脂多糖刺激的TNF-α产生低纳摩尔活性。在骨关节炎的体内大鼠碘乙酸盐模型中测试了两个类似物，并且显示出口服有效。用突变的p38α进行的X射线共结晶研究表明，这些三取代的尿素与假单双环构象的ATP结合口袋相互作用，这是由于分子内氢键相互作用的存在所致。

  DOI：

  10.1016/j.bmcl.2006.03.096

文献信息

• Tri-substituted ureas as cytokine inhibitors
  申请人：Brugel Andrew Todd

  公开号：US20050245555A1

  公开（公告）日：2005-11-03

  The present invention relates to 1,1,3-tri-substituted ureas which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 1,1,3-tri-substituted ureas which inhibit the extracellular release of inflammatory cytokines, and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.

  本发明涉及抑制炎症细胞因子的细胞外释放的1,1,3-三取代脲，该细胞因子负责一个或多个人类或高等哺乳动物疾病状态。本发明还涉及包含所述1,1,3-三取代脲的组合物，该组合物可抑制炎症细胞因子的细胞外释放，并且涉及用于预防、减轻或以其他方式控制已知为导致此处所述疾病状态的活性成分的方法。
• TRI-SUBSTITUTED UREAS AS CYTOKINE INHIBITORS
  申请人：The Procter and Gamble Company

  公开号：EP1737830A1

  公开（公告）日：2007-01-03
• US7402589B2
  申请人：——

  公开号：US7402589B2

  公开（公告）日：2008-07-22
• [EN] TRI-SUBSTITUTED UREAS AS CYTOKINE INHIBITORS<br/>[FR] UREES TRISUBSTITUEES EN TANT QU'INHIBITEURS DE CYTOKINES
  申请人：PROCTER & GAMBLE

  公开号：WO2005105757A1

  公开（公告）日：2005-11-10

  The present invention relates to 1,1,3-tri-substituted ureas having the formula (I) wherein R, R1 and R2 are as defined in the claims which inhibit the extracellular release of inflammatory cytokines, said cytokines responsible for one or more human or higher mammalian disease states. The present invention further relates to compositions comprising said 1,1,3-tri-substituted ureas which inhibit the extracellular release of inflammatory cytokines, and methods for preventing, abating, or otherwise controlling enzymes which are understood to be the active components responsible for the herein described disease states.
• Development of N-2,4-pyrimidine-N-phenyl-N′-alkyl ureas as orally active inhibitors of tumor necrosis factor alpha (TNF-α) synthesis. Part 2
  作者：Jennifer A. Maier、Todd A. Brugel、Michael P. Clark、Mark Sabat、Adam Golebiowski、Roger G. Bookland、Matthew J. Laufersweiler、Steven K. Laughlin、John C. VanRens、Biswanath De、Lily C. Hsieh、Kimberly K. Brown、Karen Juergens、Richard L. Walter、Michael J. Janusz

  DOI：10.1016/j.bmcl.2006.03.096

  日期：2006.7

  A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based on a N-2,4-pyrimidine-N-phenyl-N'-alkyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-alpha production. Two analogs were tested in an in vivo rat iodoacetate model of osteoarthritis and shown to be orally efficacious. X-ray co-crystallization

  描述了一种基于N-2，4-嘧啶-N-苯基-N'-烷基脲支架的新型肿瘤坏死因子α（TNF-α）合成抑制剂。这些化合物中有许多对脂多糖刺激的TNF-α产生低纳摩尔活性。在骨关节炎的体内大鼠碘乙酸盐模型中测试了两个类似物，并且显示出口服有效。用突变的p38α进行的X射线共结晶研究表明，这些三取代的尿素与假单双环构象的ATP结合口袋相互作用，这是由于分子内氢键相互作用的存在所致。