8-cyclopropyl-2-[(4-methylpiperazin-1-yl)methyl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one | 1169549-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 8-cyclopropyl-2-[(4-methylpiperazin-1-yl)methyl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 8-Cyclopropyl-2-[(4-methylpiperazin-1-yl)methyl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one；8-cyclopropyl-2-[(4-methylpiperazin-1-yl)methyl]-3H-[1]benzofuro[3,2-d]pyrimidin-4-one
• CAS: 1169549-49-8
• 化学式: C₁₉H₂₂N₄O₂
• 分子量: 338.409
• InChiKey: HEOZBPOPPDUPGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-2-羟基苯甲腈 在 三乙基硅烷 、 4-二甲氨基吡啶 、 potassium phosphate 、 palladium diacetate 、 caesium carbonate 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 、 三环己基膦 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 甲苯 、 乙腈 为溶剂， 反应 0.83h， 生成 8-cyclopropyl-2-[(4-methylpiperazin-1-yl)methyl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  The design, synthesis, and biological evaluation of PIM kinase inhibitors

  摘要：

  A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.025

文献信息

• [EN] BENZOFUROPYRIMIDINONES AS PROTEIN KINASE INHIBITORS<br/>[FR] BENZOFUROPYRIMIDINONES EN TANT QU'INHIBITEURS DE PROTÉINE KINASE
  申请人：EXELIXIS INC

  公开号：WO2009086264A1

  公开（公告）日：2009-07-09

  A compound according to formula I: or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3a, R3b, R3c and R3d are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

  根据公式I的化合物：或其药用可接受盐；其中R1、R2、R3a、R3b、R3c和R3d如规范中所定义，以及其药物组合物和使用方法。
• Benzofuropyrimidinones
  申请人：Brown S. David

  公开号：US20090247559A1

  公开（公告）日：2009-10-01

  A compound according to formula I: or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3a , R 3b , R 3c and R 3d are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

  公式I所示的化合物或其药学上可接受的盐；其中R1、R2、R3a、R3b、R3c和R3d如规范中所定义，以及其药物组合物和使用方法。
• BENZOFUROPYRIMIDINONES AS PROTEIN KINASE INHIBITORS
  申请人：Exelixis, Inc.

  公开号：EP2097419B1

  公开（公告）日：2011-05-25
• The design, synthesis, and biological evaluation of PIM kinase inhibitors
  作者：Amy Lew Tsuhako、David S. Brown、Elena S. Koltun、Naing Aay、Arlyn Arcalas、Vicky Chan、Hongwang Du、Stefan Engst、Maurizio Franzini、Adam Galan、Ping Huang、Stuart Johnston、Brian Kane、Moon H. Kim、A. Douglas Laird、Rui Lin、Lillian Mock、Iris Ngan、Michael Pack、Gordon Stott、Thomas J. Stout、Peiwen Yu、Cristiana Zaharia、Wentao Zhang、Peiwen Zhou、John M. Nuss、Patrick C. Kearney、Wei Xu

  DOI：10.1016/j.bmcl.2012.04.025

  日期：2012.6

  A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure. (C) 2012 Elsevier Ltd. All rights reserved.