1-[(8-bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid | 1169551-09-0

• 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: 1-[(8-bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid
• 英文别名: 1-[(8-Bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid；1-[(8-bromo-4-oxo-3H-[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid
• CAS: 1169551-09-0
• 化学式: C₁₆H₁₄BrN₃O₄
• 分子量: 392.209
• InChiKey: XQEZXMGUDOPHOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[(8-bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid 、 邻氯苯甲胺 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 异丁酰胺 为溶剂， 反应 2.0h， 以17%的产率得到1-[(8-bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]-N-[(2-chlorophenyl)methyl]pyrrolidine-3-carboxamide
  参考文献：
  名称：

  [EN] BENZOFUROPYRIMIDINONES AS PROTEIN KINASE INHIBITORS
  [FR] BENZOFUROPYRIMIDINONES EN TANT QU'INHIBITEURS DE PROTÉINE KINASE

  摘要：

  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。

  公开号：

  WO2009086264A1
• 作为产物：
  描述：

  3-氨基-5-溴苯并呋喃-2-羧酰胺 在 sodium hydroxide 作用下， 以 1,1-二氯乙烷 、 乙醇 为溶剂， 生成 1-[(8-bromo-4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)methyl]pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of XL413, a potent and selective CDC7 inhibitor

  摘要：

  CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.024

文献信息

• 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：EP2097419A1

  公开（公告）日：2009-09-09
• [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。
• Discovery of XL413, a potent and selective CDC7 inhibitor
  作者：Elena S. Koltun、Amy Lew Tsuhako、David S. Brown、Naing Aay、Arlyn Arcalas、Vicky Chan、Hongwang Du、Stefan Engst、Kim Ferguson、Maurizio Franzini、Adam Galan、Charles R. Holst、Ping Huang、Brian Kane、Moon H. Kim、Jia Li、David Markby、Manisha Mohan、Kevin Noson、Arthur Plonowski、Steven J. Richards、Scott Robertson、Kenneth Shaw、Gordon Stott、Thomas J. Stout、Jenny Young、Peiwen Yu、Cristiana A. Zaharia、Wentao Zhang、Peiwen Zhou、John M. Nuss、Wei Xu、Patrick C. Kearney

  DOI：10.1016/j.bmcl.2012.04.024

  日期：2012.6

  CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model. (C) 2012 Elsevier Ltd. All rights reserved.