4-[1-(4-Cyano-3-fluorobenzyl)-5-imidazolylmethyl]-1-[2-bromo-5-((methanesulfonyl)-oxy)benzyl]-2-piperazinone | 254108-64-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[1-(4-Cyano-3-fluorobenzyl)-5-imidazolylmethyl]-1-[2-bromo-5-((methanesulfonyl)-oxy)benzyl]-2-piperazinone
• 英文别名: [4-Bromo-3-[[4-[[3-[(4-cyano-3-fluorophenyl)methyl]imidazol-4-yl]methyl]-2-oxopiperazin-1-yl]methyl]phenyl] methanesulfonate
• CAS: 254108-64-0
• 化学式: C₂₄H₂₃BrFN₅O₄S
• 分子量: 576.446
• InChiKey: NNDBVOCETUTHSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[1-(4-Cyano-3-fluorobenzyl)-5-imidazolylmethyl]-1-[2-bromo-5-((methanesulfonyl)-oxy)benzyl]-2-piperazinone 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 caesium carbonate 、 三乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-Ethynyl-23-oxo-8-oxa-1,15,17,21-tetrazapentacyclo[19.2.2.13,7.19,13.015,19]heptacosa-3,5,7(27),9,11,13(26),16,18-octaene-10-carbonitrile
  参考文献：
  名称：

  Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

  摘要：

  A series of macrocyclic piperazinone compounds with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to be potent inhibitors of protein prenylation in cell culture. A hypothesis for the binding mode of compound 3o in FPTase is proposed. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.051
• 作为产物：
  描述：

  4-溴-3-甲基苯酚 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 三乙胺 作用下， 以 四氯化碳 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[1-(4-Cyano-3-fluorobenzyl)-5-imidazolylmethyl]-1-[2-bromo-5-((methanesulfonyl)-oxy)benzyl]-2-piperazinone
  参考文献：
  名称：

  Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

  摘要：

  A series of macrocyclic piperazinone compounds with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to be potent inhibitors of protein prenylation in cell culture. A hypothesis for the binding mode of compound 3o in FPTase is proposed. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.051

文献信息

• Inhibitors of prenyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US06562823B1

  公开（公告）日：2003-05-13

  The present invention is directed to peptidomimetic piperazine-containing macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

  本发明涉及一种含有肽类似物哌嗪的大环化合物，该化合物能抑制异戊二烯-蛋白转移酶以及致癌基因蛋白Ras的异戊二烯化作用。该发明还涉及含有本发明化合物的化疗组合物以及抑制异戊二烯-蛋白转移酶和致癌基因蛋白Ras的方法。
• US6562823B1
  申请人：——

  公开号：US6562823B1

  公开（公告）日：2003-05-13
• Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I
  作者：Christopher J Dinsmore、C.Blair Zartman、Jeffrey M Bergman、Marc T Abrams、Carolyn A Buser、J.Christopher Culberson、Joseph P Davide、Michelle Ellis-Hutchings、Christine Fernandes、Samuel L Graham、George D Hartman、Hans E Huber、Robert B Lobell、Scott D Mosser、Ronald G Robinson、Theresa M Williams

  DOI：10.1016/j.bmcl.2003.11.051

  日期：2004.2

  A series of macrocyclic piperazinone compounds with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to be potent inhibitors of protein prenylation in cell culture. A hypothesis for the binding mode of compound 3o in FPTase is proposed. (C) 2003 Elsevier Ltd. All rights reserved.