8-氧代-8H-苊并[1,2-b]吡咯-9-羧酸 | 897446-82-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 8-氧代-8H-苊并[1,2-b]吡咯-9-羧酸
• 英文名称: 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid
• 英文别名: 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carboxylic acid；8-oxoacenaphthyleno[2,1-b]pyrrole-9-carboxylic acid
• CAS: 897446-82-1
• 化学式: C₁₅H₇NO₃
• 分子量: 249.225
• InChiKey: QVYZVXCAGFXPEW-UHFFFAOYSA-N

物化性质

• 熔点：
  245 °C (decomp)(Solv: water (7732-18-5))
• 沸点：
  471.1±55.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-氧代-8H-苊并[1,2-b]吡咯-9-羧酸 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 Ethyl 8-oxo-3-thiomorpholin-4-ylacenaphthyleno[1,2-b]pyrrole-9-carboxylate
  参考文献：
  名称：

  3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1

  摘要：

  Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure-activity relationship study, and site-directed mutation, compound 6d (3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2-p4 pockets of Mcl-1, Bcl-2 and Bcl-x(L), and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC50 = 10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.008
• 作为产物：
  描述：

  1-(二氰基亚甲基)-2-氧代苊 在 硫酸 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 10.0h， 生成 8-氧代-8H-苊并[1,2-b]吡咯-9-羧酸
  参考文献：
  名称：

  3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1

  摘要：

  Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure-activity relationship study, and site-directed mutation, compound 6d (3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2-p4 pockets of Mcl-1, Bcl-2 and Bcl-x(L), and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC50 = 10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.008

文献信息

• Acenaphtho[1,2-<i>b</i>]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity
  作者：Zhuo Chen、Xin Wang、Weiping Zhu、Xianwen Cao、Linjiang Tong、Honglin Li、Hua Xie、Yufang Xu、Shaoying Tan、Dong Kuang、Jian Ding、Xuhong Qian

  DOI：10.1021/jm200258t

  日期：2011.6.9

  series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors of fibroblast growth factor receptor 1 (FGFR1) were designed and synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets of the representative compound 2, which was subsequently validated by enzyme-linked immunosorbent assay (ELISA) for its selective and active FGFR1 inhibition

  设计并合成了一系列新颖的of [1,2- b ]吡咯衍生物，作为成纤维细胞生长因子受体1（FGFR1）的有效抑制剂和选择性抑制剂。在计算机靶标中预测，酪氨酸激酶可能是代表性化合物2的潜在靶标，随后通过酶联免疫吸附测定（ELISA）验证了其对多种酪氨酸激酶的选择性和活性FGFR1抑制作用。结构-活性关系（SAR）分析通过分子对接模拟在ATP结合位点辅助证明苊并[1,2- b ]吡咯羧酸酯（2 - 5）是具有IC FGFR1的有效抑制剂50值范围从19到77 nM。此外，这些化合物对表达FGFR的癌细胞系表现出有利的生长抑制特性，其IC 50值范围从微摩尔到亚微摩尔。Western印迹分析表明，化合物2，3，和图2b FGFR1的活化抑制和细胞外信号调节激酶1/2（ERK1 / 2）。
• Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution
  作者：Fengyu Liu、Xuhong Qian、Jingnan Cui、Yi Xiao、Rong Zhang、Gangyue Li

  DOI：10.1016/j.bmc.2006.02.016

  日期：2006.7

  8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild S(N)Ar(H) reaction between 5 and

  制备了8-氧代-8H-ac并[1,2-b]吡咯-9-羧酸酯和衍生物，并评估了其对A549和P388细胞系的细胞毒性。基于新型发色团前体8-oxo-8H-ac [1,2-b]吡咯-9-腈1，将极不溶的1转化为可溶的酯5，并从5获得了一系列3-氨基衍生物通过5种胺与各种胺的温和S（N）Ar（H）反应 生物学评估表明，在母体酯5a-5f中，甲酯5a具有最高的细胞毒性，IC（50）值为0.45和0.80 microM（分别针对A549和P388），而5f的3-氨基衍生物4b和4c具有在3-氨基衍生物中，溴显示出最高的活性（IC（50）值为0.019-0.60 microM）。
• Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: Synthesis, cytotoxicity, DNA-binding and cell cycle evaluation
  作者：Lijuan Xie、Yi Xiao、Fang Wang、Yufang Xu、Xuhong Qian、Rong Zhang、Jingnan Cui、Jianwen Liu

  DOI：10.1016/j.bmc.2009.02.031

  日期：2009.11

  A family of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid derivatives were synthesized as a result of our efforts to modify a series of acenaphthopyrrole aromatic-heterocycle compounds that proved to be potent anticancer drugs. Among the derivatives, 3d (3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) and 3g (3-piperidine-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) showed potential anticancer activity and different action mechanism from our previously reported compounds. UV-vis absorption, circular dichroism and viscosity measurement indicated that effect of both compounds on the advanced DNA conformation was different, although they could bind to DNA in the same way. Cell cycle analysis showed that 3d could induce S-phase arrest followed by apoptosis, while 3g induced apoptosis. The results seem to imply that different action mechanism could contribute to the dissimilitude of biological activities toward 3d and 3g. (C) 2009 Elsevier Ltd. All rights reserved.
• 3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1
  作者：Ting Song、Xiangqian Li、Xilong Chang、Xiaomeng Liang、Yan Zhao、Guiye Wu、Shenghui Xie、Pengchen Su、Zhiyong Wu、Yingang Feng、Zhichao Zhang

  DOI：10.1016/j.bmc.2012.11.008

  日期：2013.1

  Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1), a library of 9-substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure-activity relationship study, and site-directed mutation, compound 6d (3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-3-phenyl)propylamine) was identified to span p2-p4 pockets of Mcl-1, Bcl-2 and Bcl-x(L), and then exhibited 9- to 35-fold better affinity to the three targets than 3 (IC50 = 10, 20 and 18 nM, respectively), which led to greater activity in induction of apoptosis in multiple cancer cell lines. Different contribution of p4 pocket to binding Bcl-2 and Mcl-1 was also investigated by plotting the potency and the HAC of the derivatives. (C) 2012 Elsevier Ltd. All rights reserved.