n-(5-Tert-butyl-2-methoxy-3-(methylsulfonamido)phenyl)-2-oxo-2-(4-(pyrimidin-4-ylamino)naphthalen-1-yl)acetamide | 908239-49-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: n-(5-Tert-butyl-2-methoxy-3-(methylsulfonamido)phenyl)-2-oxo-2-(4-(pyrimidin-4-ylamino)naphthalen-1-yl)acetamide
• 英文别名: N-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-2-oxo-2-[4-(pyrimidin-4-ylamino)naphthalen-1-yl]acetamide
• CAS: 908239-49-6
• 化学式: C₂₈H₂₉N₅O₅S
• 分子量: 547.635
• InChiKey: UJXXDZNSOYGBGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide 、 2-oxo-2-(4-(pyrimidin-4-ylamino)naphthalen-1-yl)acetic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 n-(5-Tert-butyl-2-methoxy-3-(methylsulfonamido)phenyl)-2-oxo-2-(4-(pyrimidin-4-ylamino)naphthalen-1-yl)acetamide
  参考文献：
  名称：

  Optimization of α-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site

  摘要：

  We have optimized a novel series of potent p38 MAP kinase inhibitors based on an alpha-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.102

文献信息

• [EN] CYTOKINE INHIBITORS AND THEIR USE IN THERAPY<br/>[FR] INHIBITEURS DES CYTOKINES ET UTILISATION THERAPEUTIQUE
  申请人：KEMIA INC

  公开号：WO2006091862A2

  公开（公告）日：2006-08-31

  [EN] The present invention relates to low molecular weight compounds and compositions thereof, useful as cytokine inhibitors, and their preparation. The invention further relates to methods of prevention and treatment of cytokine-mediated disorders, in particular inflammatory disorders, pain and cancer. The invention also relates to pharmaceutical compositions and dosing regimens. In particular, the invention relates to the use of cytokine inhibitors, optionally in conjunction with other therapies, for cancer, more particularly glioma, glioblastoma, osteosarcoma and bone metastases. Additionally, the present invention relates to methods of treating, modifying and managing pain, more particularly neuropathic pain, which comprise the administration of a cytokine inhibitor alone or in combination with known therapeutics.
  [FR] La présente invention concerne des composés de faible poids moléculaire et leurs compositions, utilisés comme inhibiteurs des cytokines, ainsi que leur préparation. L'invention concerne également des méthodes de prévention et de traitement des troubles médiés par les cytokines, en particulier les troubles inflammatoires, la douleur et le cancer. L'invention concerne également des compositions pharmaceutiques et des dosages posologiques. L'invention concerne en particulier l'utilisation des inhibiteurs des cytokines, éventuellement conjointement avec d'autres thérapies, dans le traitement du cancer, plus particulièrement du gliome, du glioblastome, de l'ostéosarcome et des métastases osseuses. La présente invention concerne, de plus, des méthodes de traitement, de modification et de gestion de la douleur, plus particulièrement des douleurs neuropathiques, consistant à administrer un inhibiteur des cytokines seul ou combiné à un traitement thérapeutique connu.
• [EN] THERAPY USING CYTOKINE INHIBITORS<br/>[FR] THERAPIE A BASE D'INHIBITEURS DE CYTOKINE
  申请人：KEMIA INC

  公开号：WO2007058990A2

  公开（公告）日：2007-05-24

  [EN] The present invention relates to methods of treating autoimmune diseases, which comprise the administration of a cytokine inhibitor alone or in combination with known therapeutics or treatments. The invention also relates to pharmaceutical compositions and dosing Tegimens. In particular, the invention relates to the use of cytokine inhibitors, optionally in conjunction with other therapies, for the treatment of autoimmune diseases, more particularly pemphigus.
  [FR] La présente invention concerne des procédés de traitement des maladies auto-immunes comprenant l'administration d'un inhibiteur de cytokine, seul ou en association avec d'autres thérapies ou traitements connus. L'invention concerne également des compositions pharmaceutiques et schémas posologiques. Plus particulièrement, l'invention concerne l'usage d'inhibiteurs de cytokine, éventuellement en association avec d'autres thérapies, dans le traitement des maladies auto-immunes et plus spécifiquement du pemphigus.
• Optimization of α-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site
  作者：Antonio Garrido Montalban、Erik Boman、Chau-Dung Chang、Susana Conde Ceide、Russell Dahl、David Dalesandro、Nancy G.J. Delaet、Eric Erb、Justin T. Ernst、Andrew Gibbs、Jeffrey Kahl、Linda Kessler、Jeff Kucharski、Christopher Lum、Jan Lundström、Stephen Miller、Hiroshi Nakanishi、Edward Roberts、Eddine Saiah、Robert Sullivan、Jan Urban、Zhijun Wang、Christopher J. Larson

  DOI：10.1016/j.bmcl.2010.06.102

  日期：2010.8

  We have optimized a novel series of potent p38 MAP kinase inhibitors based on an alpha-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions. (C) 2010 Elsevier Ltd. All rights reserved.