N-环丙基-3-[3-(1,1-二甲基乙基)-6,8-二氟-1,2,4-三唑[4,3-a]吡啶-7-基]-5-氟-4-甲基苯甲酰胺 | 1057394-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: N-环丙基-3-[3-(1,1-二甲基乙基)-6,8-二氟-1,2,4-三唑[4,3-a]吡啶-7-基]-5-氟-4-甲基苯甲酰胺
• 英文名称: 3-(3-tert-butyl-6,8-difluoro-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-N-cyclopropyl-5-fluoro-4-methylbenzamide
• CAS: 1057394-06-5
• 化学式: C₂₁H₂₁F₃N₄O
• 分子量: 402.419
• InChiKey: ZVBTZTQYHOXIBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(3,5-difluoro-4-iodopyridin-2-yl)pivalohydrazide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 叠氮基三甲基硅烷 、 caesium carbonate 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-环丙基-3-[3-(1,1-二甲基乙基)-6,8-二氟-1,2,4-三唑[4,3-a]吡啶-7-基]-5-氟-4-甲基苯甲酰胺
  参考文献：
  名称：

  Novel triazolopyridylbenzamides as potent and selective p38α inhibitors

  摘要：

  A new class of p38 alpha inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38 alpha was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38 alpha inhibitors and ultimately afforded compounds showing good in vivo efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.099

文献信息

• 3-([1,2,4]TRIAZOLO [4,3-A]PYRIDIN-7-YL)BENZAMIDE DERIVATIVES
  申请人：Vidal Juan Bernat

  公开号：US20100120731A1

  公开（公告）日：2010-05-13

  New inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) are disclosed herein, as well as processes for their preparation, pharmaceutical compositions comprising them, and their use in therapy.

  本文披露了具有一般式(I)的p38丝裂原活化蛋白激酶的新抑制剂，以及它们的制备过程，包括它们的药物组成物和在治疗中的应用。
• US8258122B2
  申请人：——

  公开号：US8258122B2

  公开（公告）日：2012-09-04
• [EN] NEW 3-([1,2,4]TRIAZOLO[4,3-A]PYRIDIN-7-YL)BENZAMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DU 3-([1,2, 4] TRIAZOLO [4,3-A] PYRIDIN-7-YL) BENZAMIDE
  申请人：ALMIRALL LAB

  公开号：WO2008107125A1

  公开（公告）日：2008-09-12

  [EN] This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.
  [FR] La présente invention porte sur de nouveaux inhibiteurs de la protéine kinase activée par le mitogène p38 selon la formule générale (I) et sur leurs procédés de préparation, ainsi que sur les compositions pharmaceutiques les incluant et sur leur utilisation dans le cadre d'un traitement.
• Novel triazolopyridylbenzamides as potent and selective p38α inhibitors
  作者：Josep Aiguadé、Cristina Balagué、Inés Carranco、Francisco Caturla、María Domínguez、Paul Eastwood、Cristina Esteve、Jacob González、Wenceslao Lumeras、Adelina Orellana、Sara Preciado、Ramón Roca、Laura Vidal、Bernat Vidal

  DOI：10.1016/j.bmcl.2012.03.099

  日期：2012.5

  A new class of p38 alpha inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38 alpha was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38 alpha inhibitors and ultimately afforded compounds showing good in vivo efficacy. (C) 2012 Elsevier Ltd. All rights reserved.