6-tert-butyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione | 890664-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 6-tert-butyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione
• CAS: 890664-87-6
• 化学式: C₁₀H₁₁NO₃S
• 分子量: 225.268
• InChiKey: DICQENVVMISBOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-tert-butyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 1-(5-tert-butylthiophen-2-yl)-3-(1H-indazol-5-yl)urea
  参考文献：
  名称：

  Potent and selective thiophene urea-templated inhibitors of S6K

  摘要：

  S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of obesity and insulin resistance, thus making it an attractive target in developing medicines for the treatment of these disorders. We describe a novel thiophene urea class of S6K inhibitors. The lead matter for the development of these inhibitors came from mining the literature for reports of weak off-target S6K activity. These optimized inhibitors exhibit good potency and excellent selectivity for S6K over a panel of 43 kinases. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.069
• 作为产物：
  描述：

  3,3-二甲基丁醛 在 水 、 sulfur 、 三乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 6-tert-butyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  Potent and selective thiophene urea-templated inhibitors of S6K

  摘要：

  S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of obesity and insulin resistance, thus making it an attractive target in developing medicines for the treatment of these disorders. We describe a novel thiophene urea class of S6K inhibitors. The lead matter for the development of these inhibitors came from mining the literature for reports of weak off-target S6K activity. These optimized inhibitors exhibit good potency and excellent selectivity for S6K over a panel of 43 kinases. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.069

文献信息

• UREA INHIBITORS OF MAP KINASES
  申请人：NGUYEN Duyan

  公开号：US20100041642A1

  公开（公告）日：2010-02-18

  Urea containing compounds that inhibit MAP kinases, pharmaceutical compositions including such compounds and methods for using these compounds to treat inflammatory diseases and cancer are described herein.

  本文描述了含有抑制MAP激酶的尿素类化合物、包括这些化合物的药物组合物以及使用这些化合物治疗炎症性疾病和癌症的方法。
• 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。
• Inhibitors of protein kinases
  申请人：Michelotti Luis Enrique

  公开号：US20070185098A1

  公开（公告）日：2007-08-09

  The present invention is directed to a compound having the formula wherein R 1 , R 2 , R 3 , R 4 , G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to compounds that stabilize the open conformation of a protein kinase, a crystallized protein kinase in the open conformation, and uses thereof. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease.

  本发明涉及一种具有以下式子的化合物，其中R1、R2、R3、R4、G和Q在此定义。本发明的化合物可用作蛋白激酶的抑制剂。本发明还涉及包含上述式子的化合物的组合物。本发明还涉及稳定蛋白激酶开放构象的化合物、晶化的蛋白激酶在开放构象下的化合物和使用它们的方法。本文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。
• INHIBITORS OF PROTEIN KINASES
  申请人：Michelotti Enrique Luis

  公开号：US20090192307A1

  公开（公告）日：2009-07-30

  The present invention is directed to a compound having the formula wherein R 1 , R 2 , R 3 , R 4 , G, and Q are defined herein. The compounds of the present invention are useful as inhibitors of protein kinases. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to compounds that stabilize the open conformation of a protein kinase, a crystallized protein kinase in the open conformation, and uses thereof. The compounds and compositions described herein are useful for treating and preventing an inflammatory condition or disease.

  本发明涉及一种具有以下式子的化合物，其中R1、R2、R3、R4、G和Q如下所定义。本发明的化合物可用作蛋白激酶抑制剂。本发明还涉及包含上述式子中的化合物的组合物。本发明还涉及稳定蛋白激酶开放构象的化合物，以及开放构象的结晶蛋白激酶和其用途。本发明所描述的化合物和组合物可用于治疗和预防炎症性疾病或病症。
• 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.