2-(4-(5-tert-butyl-2-(3-(2,3-dichlorophenyl)ureido)thiophene-3-carbonyl)-7-oxo-1,4-diazepan-1-yl)acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 2-(4-(5-tert-butyl-2-(3-(2,3-dichlorophenyl)ureido)thiophene-3-carbonyl)-7-oxo-1,4-diazepan-1-yl)acetamide
• 英文别名: 2-(4-{5-tert-butyl-2-[3-(2,3-dichlorophenyl)ureido]thiophene-3-carbonyl}-7-oxo-[1,4]diazepan-1-yl)acetamide；2-[4-[5-Tert-butyl-2-[(2,3-dichlorophenyl)carbamoylamino]thiophene-3-carbonyl]-7-oxo-1,4-diazepan-1-yl]acetamide
• 化学式: C₂₃H₂₇Cl₂N₅O₄S
• 分子量: 540.47
• InChiKey: AGNVPTNJYSCESG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-Cbz-[1,4]二氮杂庚烷-5-酮 在 palladium 10% on activated carbon 、 氨 、 氢气 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 2-(4-(5-tert-butyl-2-(3-(2,3-dichlorophenyl)ureido)thiophene-3-carbonyl)-7-oxo-1,4-diazepan-1-yl)acetamide
  参考文献：
  名称：

  Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

  摘要：

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2011.09.078

文献信息

• Urea inhibitors of MAP kinases
  申请人：Michelotti Luis Enrique

  公开号：US20060167247A1

  公开（公告）日：2006-07-27

  The present invention is directed to a compound having the formula wherein R 1 , R 2 , G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases such as MAP kinases, in particular p38 kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease. The present invention is also directed to a method of treating or preventing a protein kinase-mediated condition.

  本发明涉及一种化合物，其具有以下式子：其中R1、R2、G和Q在此处定义。本发明的化合物可用作蛋白激酶的抑制剂，例如MAP激酶，特别是p38激酶。本发明还涉及包含上述式子化合物的组合物。本发明所描述的化合物和组合物可用于治疗和预防炎症状况或疾病。本发明还涉及一种治疗或预防蛋白激酶介导病症的方法。
• UREA INHIBITORS OF MAP KINASES
  申请人：Locus Pharmaceuticals, Inc.

  公开号：EP1828169A2

  公开（公告）日：2007-09-05
• US7741479B2
  申请人：——

  公开号：US7741479B2

  公开（公告）日：2010-06-22
• [EN] UREA INHIBITORS OF MAP KINASES<br/>[FR] INHIBITEURS URÉE DE MAP KINASES
  申请人：LOCUS PHARMACEUTICALS INC

  公开号：WO2006062982A2

  公开（公告）日：2006-06-15

  [EN] The present invention is directed to a compound having the formula (I) wherein R¹, R², G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases such as MAP Kinases, in particular p38 kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease. The present invention is also directed to a method of treating or preventing a protein kinase-mediated condition.
  [FR] Composé de formule (I) dans laquelle R¹, R², G et Q sont définis dans le descriptif. Lesdits composés sont utiles en tant qu'inhibiteurs de protéine kinases telles que les MAP kinases, en particulier les p38 kinases. La présente invention concerne également des compositions contenant un composé de formule ci-dessus. Les composés et compositions décrits sont utiles pour traiter et prévenir des états ou maladies inflammatoires. La présente invention concerne en outre une méthode de traitement ou de prévention d'un état pathologique à médiation par les protéine kinases.
• Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)
  作者：Kristofer Moffett、Zenon Konteatis、Duyan Nguyen、Rupa Shetty、Jennifer Ludington、Ted Fujimoto、Kyoung-Jin Lee、Xiaomei Chai、Haridasan Namboodiri、Michael Karpusas、Bruce Dorsey、Frank Guarnieri、Marina Bukhtiyarova、Eric Springman、Enrique Michelotti

  DOI：10.1016/j.bmcl.2011.09.078

  日期：2011.12

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.