tert-butyl (Z)-4-({2-[(1H-indazol-3-yl)methylene]-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate | 1346151-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl (Z)-4-({2-[(1H-indazol-3-yl)methylene]-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate
• 英文别名: (Z)-tert-butyl 4-((2-((1H-indazol-3-yl)methylene)-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl)piperazine-1-carboxylate；tert-butyl 4-[[(2Z)-2-(2H-indazol-3-ylmethylidene)-6-methoxy-3-oxo-1-benzofuran-7-yl]methyl]piperazine-1-carboxylate
• CAS: 1346151-98-1
• 化学式: C₂₇H₃₀N₄O₅
• 分子量: 490.559
• InChiKey: AIFNYBFPWRIKMF-HAHDFKILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.24
• 重原子数：
  36.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  96.99
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (Z)-4-({2-[(1H-indazol-3-yl)methylene]-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate 在 三氟乙酸 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以8%的产率得到(Z)-2-((1H-indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one
  参考文献：
  名称：

  ANTICANCER AGENT

  摘要：

  公开号：

  EP2565192B9
• 作为产物：
  描述：

  tert-butyl 4-((6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl)piperazine-1-carboxylate 在 哌啶 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 4.0h， 生成 tert-butyl (Z)-4-({2-[(1H-indazol-3-yl)methylene]-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl}methyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis of (Z)-2-((1H-indazol-3-yl)methylene)-6-[11C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one as a new potential PET probe for imaging of the enzyme PIM1

  摘要：

  (Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC50 value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[C-11]methoxy-7-(piperazin-1-ylmethyl) benzofuran-3(2H)-one, a new potential PET probe for imaging of the enzyme PIM1, was first designed and synthesized in 20-30% decay corrected radiochemical yield and 370-740 GBq/mu mol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled Boc-protected intermediate followed by a quick acidic de-protection. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.091

文献信息

• Anticancer agent
  申请人：Nagano Tetsuo

  公开号：US09156827B2

  公开（公告）日：2015-10-13

  An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6 alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; R4 represents hydrogen atom, a C1-6 alkyl group, a C1-6 alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6 alkyl group and the like; R8 represents hydrogen atom, a C1-6 alkyl group and the like; A represents —O—, —S—, or —CH2—; D represents —C═ or —N═; X represents methylene group, —O—, or —CO—; Q represents —N═ or —C(R8)═; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.

  一种抗癌剂，包括由公式（I）所代表的化合物 [ R1 代表氢原子、羟基、C1-6烷氧基等； R2 和 R3 代表氢原子、卤素原子、C1-6烷基等； R4 代表氢原子、C1-6烷基、C1-6烷基磺酰基等； R5 代表氢原子或取代基； 表示单键或双键； R6 和 R7 代表氢原子、C1-6烷基等； R8 代表氢原子、C1-6烷基等； A 代表-O-、-S-或-CH2-； D 代表-C═或-N═； X 代表亚甲基基、-O-或-CO-； Q 代表-N═或-C(R8)═； Y 代表杂环基或氨基]，该化合物对pim-1激酶具有卓越的抑制活性。
• Rational Evolution of a Novel Type of Potent and Selective Proviral Integration Site in Moloney Murine Leukemia Virus Kinase 1 (PIM1) Inhibitor from a Screening-Hit Compound
  作者：Hirofumi Nakano、Nae Saito、Lorien Parker、Yukio Tada、Masanao Abe、Keiko Tsuganezawa、Shigeyuki Yokoyama、Akiko Tanaka、Hirotatsu Kojima、Takayoshi Okabe、Tetsuo Nagano

  DOI：10.1021/jm3001289

  日期：2012.6.14

  Serine/threonine kinase PIM1 is an emerging therapeutic target for hematopoietic and prostate cancer therapy. To develop a novel PIM1 inhibitor, we focused on 1, a metabolically labile, nonselective kinase inhibitor discovered in our previous screening study. We adopted a rational optimization strategy based mainly on structural information for the PIM1-1 complex to improve the potency and selectivity. This approach afforded the potent and metabolically stable PIM1-selective inhibitor 14, which shows only a marginal increase in molecular weight compared with 1 but has a significantly decreased cLogP. The validity of our design concept was confirmed by X-ray structure analysis. In a cellular study, 14 potently inhibited the growth of human leukemia cell line MV4-11 but had a negligible effect on the growth of WI-38 (surrogate for general toxicity). These results demonstrate the effectiveness of our design strategy for evolving the screening-hit compound 1 into a novel type of PIM1 inhibitor, 14.
• ANTICANCER AGENT
  申请人：The University of Tokyo

  公开号：EP2565192B9

  公开（公告）日：2015-11-25
• Synthesis of (Z)-2-((1H-indazol-3-yl)methylene)-6-[11C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one as a new potential PET probe for imaging of the enzyme PIM1
  作者：Mingzhang Gao、Min Wang、Kathy D. Miller、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2013.05.091

  日期：2013.8

  (Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC50 value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[C-11]methoxy-7-(piperazin-1-ylmethyl) benzofuran-3(2H)-one, a new potential PET probe for imaging of the enzyme PIM1, was first designed and synthesized in 20-30% decay corrected radiochemical yield and 370-740 GBq/mu mol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled Boc-protected intermediate followed by a quick acidic de-protection. (C) 2013 Elsevier Ltd. All rights reserved.