5-[(1E)-buta-1,3-dien-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile | 1160916-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-[(1E)-buta-1,3-dien-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile
• 英文别名: 5-[(1E)-buta-1,3-dienyl]-4-[(4-methyl-1H-indol-5-yl)amino]pyridine-3-carbonitrile
• CAS: 1160916-38-0
• 化学式: C₁₉H₁₆N₄
• 分子量: 300.363
• InChiKey: PZLSUIJNWJPJTM-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  64.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl 4-methylbenzenesulfonate 、 5-iodo-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 在 吲哚啉 、 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以26%的产率得到5-[(1E)-buta-1,3-dien-yl]-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile
  参考文献：
  名称：

  5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCθ: Optimization of enzymatic and functional activity

  摘要：

  PKC theta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKC theta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with Log D(7.4), but not with c Log P, PAMPA permeability, or TPSA. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.10.020

文献信息

• [EN] 5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS<br/>[FR] 5-ALKYL/ALCÉNYL-3-CYANOPYRIDINES EN TANT QU'INHIBITEURS DE KINASE
  申请人：WYETH CORP

  公开号：WO2009076602A8

  公开（公告）日：2010-02-18
• 5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2229377A1

  公开（公告）日：2010-09-22
• 5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCθ: Optimization of enzymatic and functional activity
  作者：L. Nathan Tumey、Niala Bhagirath、Agnes Brennan、Natasja Brooijmans、Julie Lee、Xiaoke Yang、Diane H. Boschelli

  DOI：10.1016/j.bmc.2009.10.020

  日期：2009.12

  PKC theta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKC theta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with Log D(7.4), but not with c Log P, PAMPA permeability, or TPSA. (c) 2009 Elsevier Ltd. All rights reserved.