N-(5-tert-butyl-3-cyano-2-methoxyphenyl)-2-(4-(6-fluoropyridin-3-yl)naphthalen-1-yl)-2-oxoacetamide | 1041051-68-6

• 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-3-cyano-2-methoxyphenyl)-2-(4-(6-fluoropyridin-3-yl)naphthalen-1-yl)-2-oxoacetamide
• 英文别名: N-(5-tert-butyl-3-cyano-2-methoxyphenyl)-2-[4-(6-fluoropyridin-3-yl)naphthalen-1-yl]-2-oxoacetamide
• CAS: 1041051-68-6
• 化学式: C₂₉H₂₄FN₃O₃
• 分子量: 481.526
• InChiKey: DLIGLZOVDFBTKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-amino-5-(tert-butyl)-2-methoxybenzonitrile 、 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-3-cyano-2-methoxyphenyl)-2-(4-(6-fluoropyridin-3-yl)naphthalen-1-yl)-2-oxoacetamide
  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<br/>[FR] INHIBITEURS DE CYTOKINE
  申请人：KEMIA INC

  公开号：WO2008089034A2

  公开（公告）日：2008-07-24

  [EN] The present invention provides low molecular weight compounds useful as cytokine inhibitors, and compositions thereof. In particular, compounds of the invention are useful as anti-inflammatory agents. There are further provided methods for the preparation of such agents and their use in preventing or treating conditions mediated by cytokines, such as for example arthritis, pain, cardiovascular disease and cancer.
  [FR] La présente invention concerne des composés de faible masse moléculaire utiles comme inhibiteurs de cytokine et des compositions de ceux-ci. En particulier, des composés de l'invention sont utiles comme agents anti-inflammatoires. Il est en outre proposé des procédés pour la préparation de tels agents et leur utilisation pour la prévention ou le traitement d'affections véhiculées par des cytokines, telles que par exemple l'arthrite, la douleur, la maladie cardiovasculaire et le cancer.
• 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.