4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine | 1247000-95-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine
• 英文别名: 4-fluoro-1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidine
• CAS: 1247000-95-8
• 化学式: C₁₈H₂₇BFNO₂
• 分子量: 319.227
• InChiKey: XKPNRWPTPLMDDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-(3-iodo-1H-indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one 、 4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 (1R,2S)-5'-methoxy-2-(3-(4-(4-fluoro-1-methylpiperidin-4-yl)phenyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one
  参考文献：
  名称：

  Design and optimization of (3-aryl-1 H -indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-ones as potent PLK4 inhibitors with oral antitumor efficacy

  摘要：

  Previous efforts from our laboratory demonstrated that (E)-3-((3-(E)-vinylaryl)-1H-indazol-6-yl) methylene)-indolin-2-ones are potent PLK4 inhibitors with in vivo anticancer efficacy upon IP dosing. As part of a continued effort to develop selective and orally efficacious inhibitors, we examined variations on this theme wherein 'directly-linked' aromatics, pendant from the indazole core, replace the arylvinyl moiety. Herein, we describe the design and optimization of this series which was ultimately superseded by (3-aryl-1H-indazol-6-yl) spiro[cyclopropane-1,30-indolin]-20-ones. The latter compounds are potent and selective inhibitors of PLK4 with oral exposure in rodents and in vivo anticancer activity. Compound 13b, in particular, has a bioavailability of 22% and achieved a 96% tumor growth inhibition in an MDA-MB-468 xenograft study. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.08.063
• 作为产物：
  描述：

  1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidin-4-yl acetate 、 4-(4-bromophenyl)-4-fluoro-1-methylpiperidine 在 4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine 、 乙酸乙酯 、 Brine 、 magnesium sulfate 作用下， 以 乙酸乙酯 、 水 为溶剂， 以to give the title compound as a brown solid (281 mg, used without further purification)的产率得到4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine
  参考文献：
  名称：

  Kinase inhibitors and method of treating cancer with same

  摘要：

  本发明涉及一种由以下结构式表示的化合物及其药学上可接受的盐：该结构式表示的化合物是激酶抑制剂，因此在此披露用于治疗癌症。该结构式中各变量的定义在此提供。

  公开号：

  US08481525B2
• 作为试剂：
  描述：

  1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidin-4-yl acetate 、 4-(4-bromophenyl)-4-fluoro-1-methylpiperidine 在 4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine 、 乙酸乙酯 、 Brine 、 magnesium sulfate 作用下， 以 乙酸乙酯 、 水 为溶剂， 以to give the title compound as a brown solid (281 mg, used without further purification)的产率得到4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine
  参考文献：
  名称：

  KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME

  摘要：

  本发明涉及以下结构式及其药物可接受的盐所表示的化合物：该结构式所表示的化合物是激酶抑制剂，因此在此披露用于治疗癌症。本结构式中变量的定义在此提供。

  公开号：

  US20120149686A1

文献信息

• Kinase inhibitors and method of treating cancer
  申请人：University Health Network

  公开号：US08263596B2

  公开（公告）日：2012-09-11

  The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

  该发明涉及以下结构式及其药学上可接受的盐所表示的化合物：此结构式所表示的化合物是激酶抑制剂，因此在此透露用于治疗癌症。此处提供了结构式中变量的定义。
• Kinase inhibitors and method of treating cancer with same
  申请人：Sampson Peter Brent

  公开号：US08481525B2

  公开（公告）日：2013-07-09

  The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

  本发明涉及一种由以下结构式表示的化合物及其药学上可接受的盐：该结构式表示的化合物是激酶抑制剂，因此在此披露用于治疗癌症。该结构式中各变量的定义在此提供。
• Design and optimization of (3-aryl-1 H -indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-ones as potent PLK4 inhibitors with oral antitumor efficacy
  作者：Sze-Wan Li、Yong Liu、Peter B. Sampson、Narendra Kumar Patel、Bryan T. Forrest、Louise Edwards、Radoslaw Laufer、Miklos Feher、Fuqiang Ban、Donald E. Awrey、Richard Hodgson、Irina Beletskaya、Guodong Mao、Jacqueline M. Mason、Xin Wei、Xunyi Luo、Reza Kiarash、Erin Green、Tak W. Mak、Guohua Pan、Henry W. Pauls

  DOI：10.1016/j.bmcl.2016.08.063

  日期：2016.10

  Previous efforts from our laboratory demonstrated that (E)-3-((3-(E)-vinylaryl)-1H-indazol-6-yl) methylene)-indolin-2-ones are potent PLK4 inhibitors with in vivo anticancer efficacy upon IP dosing. As part of a continued effort to develop selective and orally efficacious inhibitors, we examined variations on this theme wherein 'directly-linked' aromatics, pendant from the indazole core, replace the arylvinyl moiety. Herein, we describe the design and optimization of this series which was ultimately superseded by (3-aryl-1H-indazol-6-yl) spiro[cyclopropane-1,30-indolin]-20-ones. The latter compounds are potent and selective inhibitors of PLK4 with oral exposure in rodents and in vivo anticancer activity. Compound 13b, in particular, has a bioavailability of 22% and achieved a 96% tumor growth inhibition in an MDA-MB-468 xenograft study. (C) 2016 Elsevier Ltd. All rights reserved.
• KINASE INHIBITORS AND METHOD OF TREATING CANCER
  申请人：Sampson Peter B.

  公开号：US20110263598A1

  公开（公告）日：2011-10-27

  The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

  本发明涉及以下结构式和其药学上可接受的盐所代表的化合物：该结构式所代表的化合物是激酶抑制剂，因此本发明公开了用于治疗癌症的该类化合物。该结构式中变量的定义在此提供。
• KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
  申请人：Sampson Peter B.

  公开号：US20120149686A1

  公开（公告）日：2012-06-14

  The invention is directed to a compound represented by the following structural formula and pharmaceutically acceptable salts thereof: Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.

  本发明涉及以下结构式及其药物可接受的盐所表示的化合物：该结构式所表示的化合物是激酶抑制剂，因此在此披露用于治疗癌症。本结构式中变量的定义在此提供。