6,11-dioxo-6,11-dihydrobenzo[f]pyrido[1,2-a]indole-12-carboxylic acid | 109964-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6,11-dioxo-6,11-dihydrobenzo[f]pyrido[1,2-a]indole-12-carboxylic acid
• 英文别名: 6,11-dioxonaphtho[2,3-b]indolizine-12-carboxylic acid
• CAS: 109964-49-0
• 化学式: C₁₇H₉NO₄
• mdl: MFCD02323201
• 分子量: 291.263
• InChiKey: IWTDBHRFVHGMBT-UHFFFAOYSA-N

物化性质

• 熔点：
  313-314 °C
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 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：
  75.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,11-dioxo-6,11-dihydrobenzo[f]pyrido[1,2-a]indole-12-carboxylic acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氯化碳 、 乙腈 为溶剂， 生成 isopropyl 6,11-dioxo-6,11- dihydrobenzo[f]pyrido[1,2-a]indole-12-carboxylate
  参考文献：
  名称：

  6,11-Dioxobenzo[f]pyrido[1,2-a]indoles Kill Mycobacterium tuberculosis by Targeting Iron–Sulfur Protein Rv0338c (IspQ), A Putative Redox Sensor

  摘要：

  Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[f]pyrido[1,2-a]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of Mycobacterium tuberculosis in vitro. The activity of these hit compounds was limited to tubercle bacilli, including the nonreplicating form, and to Mycobacterium marinum. On hit expansion and investigation of the structure activity relationship, selected modifications to the dioxo moiety of the DBPI scaffold were either neutral or led to reduction or abolition of antimycobacterial activity. To find the target, DBPI-resistant mutants of M. tuberculosis Erdman were raised and characterized first microbiologically and then by whole genome sequencing. Four different mutations, all affecting highly conserved residues, were uncovered in the essential gene rv0338c (ispQ) that encodes a membrane-bound protein, named IspQ, with 2Fe-2S and 4Fe-4S centers and putative iron-sulfur-binding reductase activity. With the help of a structural model, two of the mutations were localized close to the 2Fe-2S domain in IspQ and another in transmembrane segment 3. The mutant genes were recessive to the wild type in complementation experiments and further confirmation of the hit-target relationship was obtained using a conditional knockdown mutant of rv0338c in M. tuberculosis H37Rv. More mechanistic insight was obtained from transcriptome analysis, following exposure of M. tuberculosis to two different DBPI; this revealed strong upregulation of the redox-sensitive SigK regulon and genes induced by oxidative and thiol-stress. The findings of this investigation pharmacologically validate a novel target in tubercle bacilli and open a new vista for tuberculosis drug discovery.

  DOI：

  10.1021/acsinfecdis.0c00531
• 作为产物：
  描述：

  1-吡啶-2-基-2-丙酮 在 吡啶 、 sodium hydroxide 、 乙醇 、 碘 、 sodium ethanolate 作用下， 生成 6,11-dioxo-6,11-dihydrobenzo[f]pyrido[1,2-a]indole-12-carboxylic acid
  参考文献：
  名称：

  Reactions of Naphthoquinones with Malonic Ester and its Analogs. III. 1-Substituted Phthaloyl- and Phthaloylbenzopyrrocolines¹

  摘要：

  DOI：

  10.1021/ja01562a048

文献信息

• Design, synthesis and structure-activity relationship study of novel naphthoindolizine and indolizinoquinoline-5,12-dione derivatives as IDO1 inhibitors
  作者：Rui Yang、Yu Chen、Liangkun Pan、Yanyan Yang、Qiang Zheng、Yue Hu、Yuxi Wang、Liangren Zhang、Yang Sun、Zhongjun Li、Xiangbao Meng

  DOI：10.1016/j.bmc.2018.08.028

  日期：2018.9

  Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as a promising target for cancer immunotherapy. Many naphthoquinone derivatives have been reported as IDO1 inhibitors so far. Herein, two series of naphthoquinone derivatives, naphthoindolizine and indolizinoquinoline-5,12-dione derivatives, were synthesized and evaluated for their IDO1 inhibitory activity. Most of the target compounds showed significant

  吲哚胺 2,3-双加氧酶 1 (IDO1) 被认为是癌症免疫治疗的一个有希望的靶点。迄今为止，许多萘醌衍生物已被报道为 IDO1 抑制剂。在此，合成了两个系列的萘醌衍生物，naphthoindolizine 和 indolizinoquinoline-5,12-dione 衍生物，并评估了它们的 IDO1 抑制活性。与色氨酸 2,3-双加氧酶 (TDO) 相比，大多数目标化合物对 IDO1 显示出显着的抑制效力和高选择性。还总结了构效关系。最有效的化合物5c（IC 50 23 nM，IDO1 酶）和5b'（IC 50 372 nM，HeLa 细胞）被鉴定为有前景的先导化合物。
• Acharya et al., Journal Of Scientific and Industrial Research, 1958, vol. 17 B, p. 483,490
  作者：Acharya et al.

  DOI：——

  日期：——
• BIOLOGICAL ACTIVITIES AND CORRELATIONS TENDENCY OF ELECTROCHEMICAL PROPERTIES OF SOME INDOLIZINO[1,2-B]QUINOLINE DERIVATIVES
  作者：A CAÑETE、F ARMIJO、M. A DEL VALLE、R.A TAPIA、C THEODULOZ、C. D PESSOA、L CANTUARIAS、G RECABARREN

  DOI：10.4067/s0717-97072012000200015

  日期：——

  We report the preparation of a series of indolylquinone and pyridine derivatives in order to evaluate structure-activity relationships in human gastric (AGS), lung (SK-MES-1), bladder (J82) cancer cell lines and human normal lung fibroblasts (MCR-5). Two correlations tendency between half-wave redox potentials against their antineoplasic activity were found making it possible to establish that for epithelial human gastric cancer (AGS) cell lines and human normal lung fibroblasts (MCR-5). The quinone bioreduction should correspond to a one electron process under normomix conditions, whilst for all other lines this process should correspond to a two electron attachment via a hypoxic process.
• Mathur; Tilak, Journal Of Scientific and Industrial Research, 1958, vol. 17 B, p. 33,38
  作者：Mathur、Tilak

  DOI：——

  日期：——
• Suryanarayana; Tilak, Proceedings - Indian Academy of Sciences, Section A, 1954, vol. 39, p. 185,194
  作者：Suryanarayana、Tilak

  DOI：——

  日期：——