3-Fluoro-3-(4-nitro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2,6-dioxo-piperidine-1-carboxylic acid tert-butyl ester | 625852-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-Fluoro-3-(4-nitro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2,6-dioxo-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 3-fluoro-3-(4-nitro-1,3-dioxoisoindol-2-yl)-2,6-dioxopiperidine-1-carboxylate；tert-butyl 3-fluoro-3-(4-nitro-1,3-dioxoisoindol-2-yl)-2,6-dioxopiperidine-1-carboxylate
• CAS: 625852-90-6
• 化学式: C₁₈H₁₆FN₃O₈
• 分子量: 421.339
• InChiKey: YGTOXPPWOMUFKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  147
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-Fluoro-3-(4-nitro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2,6-dioxo-piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 α-F N-Boc-pomalidomide
  参考文献：
  名称：

  α-Fluoro-substituted thalidomide analogues

  摘要：

  Thalidomide, (1), has made a remarkable comeback from its days of a sedative with teratogenic properties due to its ability to selectively inhibit TNF-alpha, a key pro-inflammatory cytokine and its clinical benefit in the treatment of cancer. Thalidomide contains one chiral center and is known to be chirally unstable under in vitro and in vivo conditions. It has been hypothesized that different biological properties are associated with each isomer. Thus, chirally stable analogues of thalidomide, alpha-fluorothalidomide, (3) and alpha-fluoro-4-aminothalidomide (4) were prepared by electrophilic fluorination. Analogue 3 was found to be cytotoxic and did not inhibit TNF-alpha production in LPS stimulated hPBMC below toxic concentrations. On the other hand, 4 was non-cytotoxic at the tested concentrations and was found to be 830-fold more potent than thalidomide as TNF-alpha inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00778-9
• 作为产物：
  描述：

  1,3-二氧-2-( 2,6-二氧哌啶-3-基) -5-硝基异二氢吲哚 在 4-二甲氨基吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 3-Fluoro-3-(4-nitro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2,6-dioxo-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  α-Fluoro-substituted thalidomide analogues

  摘要：

  Thalidomide, (1), has made a remarkable comeback from its days of a sedative with teratogenic properties due to its ability to selectively inhibit TNF-alpha, a key pro-inflammatory cytokine and its clinical benefit in the treatment of cancer. Thalidomide contains one chiral center and is known to be chirally unstable under in vitro and in vivo conditions. It has been hypothesized that different biological properties are associated with each isomer. Thus, chirally stable analogues of thalidomide, alpha-fluorothalidomide, (3) and alpha-fluoro-4-aminothalidomide (4) were prepared by electrophilic fluorination. Analogue 3 was found to be cytotoxic and did not inhibit TNF-alpha production in LPS stimulated hPBMC below toxic concentrations. On the other hand, 4 was non-cytotoxic at the tested concentrations and was found to be 830-fold more potent than thalidomide as TNF-alpha inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00778-9

文献信息

• α-Fluoro-substituted thalidomide analogues
  作者：Hon-Wah Man、Laura G Corral、David I Stirling、George W Muller

  DOI：10.1016/s0960-894x(03)00778-9

  日期：2003.10

  Thalidomide, (1), has made a remarkable comeback from its days of a sedative with teratogenic properties due to its ability to selectively inhibit TNF-alpha, a key pro-inflammatory cytokine and its clinical benefit in the treatment of cancer. Thalidomide contains one chiral center and is known to be chirally unstable under in vitro and in vivo conditions. It has been hypothesized that different biological properties are associated with each isomer. Thus, chirally stable analogues of thalidomide, alpha-fluorothalidomide, (3) and alpha-fluoro-4-aminothalidomide (4) were prepared by electrophilic fluorination. Analogue 3 was found to be cytotoxic and did not inhibit TNF-alpha production in LPS stimulated hPBMC below toxic concentrations. On the other hand, 4 was non-cytotoxic at the tested concentrations and was found to be 830-fold more potent than thalidomide as TNF-alpha inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.