3-thioxo-2,3-dihydroimidazo[1,5-b]isoquinoline-1,5-dione | 96117-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-thioxo-2,3-dihydroimidazo[1,5-b]isoquinoline-1,5-dione
• 英文别名: 3-Thioxo-2h-imidazo[1,5-b]isoquinoline-1,5-dione；3-sulfanylideneimidazo[1,5-b]isoquinoline-1,5-dione
• CAS: 96117-98-5
• 化学式: C₁₁H₆N₂O₂S
• 分子量: 230.247
• InChiKey: CINQTZPMWMGMEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-thioxo-2,3-dihydroimidazo[1,5-b]isoquinoline-1,5-dione 在 sodium tetrahydroborate 、 nickel dichloride 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以75%的产率得到2,3-dihydroimidazo[1,5-b]isoquinoline-1,5-dione
  参考文献：
  名称：

  A novel synthesis of 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones by in situ desulfurization

  摘要：

  A novel synthesis of 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones by reductive desulfurization of a variety of 2-substituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones is reported with nickel boride in dry methanol at ambient temperature.

  DOI：

  10.1007/s10593-008-0045-1
• 作为产物：
  描述：

  2-硫代乙内酰脲 、 2-(二甲氧基甲基)苯甲酸甲酯 在 sodium acetate 、 溶剂黄146 作用下， 反应 4.0h， 以68%的产率得到3-thioxo-2,3-dihydroimidazo[1,5-b]isoquinoline-1,5-dione
  参考文献：
  名称：

  Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family

  摘要：

  The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and 1(562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC55 of 0.75 mu M against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.02.056

文献信息

• Total synthesis and structural revision of a mangrove alkaloid
  作者：Michael T. Green、Gary R. Peczkowski、Aneesa J. Al-Ani、Sophie L. Benjamin、Nigel S. Simpkins、Alan M. Jones

  DOI：10.1039/c7ra10483a

  日期：——

  We report the total synthesis of an alkaloid isolated from the mangrove fungi Hypocrea virens, based on the originally claimed structure, via a photochemical sequence. Inconsistencies between data sets led to a revision of the proposed structure followed by a concise synthetic sequence to deliver the revised natural product.

  我们报告了从原始的要求保护的结构，通过光化学序列，从红树林真菌Hypocrea virens分离出的生物碱的总合成。数据集之间的不一致导致对提议的结构进行了修订，随后是简明的合成顺序以交付经过修订的天然产品。
• Camptothecin structure simplification elaborated new imidazo[2,1-b]quinazoline derivative as a human topoisomerase I inhibitor with efficacy against bone cancer cells and colon adenocarcinoma
  作者：Ahmed I. Khodair、Salwa M. El-Hallouty、Brittnee Cagle-White、May H. Abdel Aziz、Mahmoud Kh. Hanafy、Samar Mowafy、Nadia M. Hamdy、Shaymaa E. Kassab

  DOI：10.1016/j.ejmech.2023.116049

  日期：2024.2

  Camptothecin is a pentacyclic natural alkaloid that inhibits the hTop1 enzyme involved in DNA transcription and cancer cell growth. Camptothecin structure pitfalls prompted us to design new congeners using a structure simplification strategy to reduce the ring extension number from pentacyclic to tetracyclic while maintaining potential stacking of the new compounds with the DNA base pairs at the Top1-mediated

  喜树碱是一种五环天然生物碱，可抑制参与 DNA 转录和癌细胞生长的 hTop1 酶。喜树碱结构缺陷促使我们使用结构简化策略设计新的同系物，以减少从五环到四环的环延伸数，同时保持新化合物与 Top1 介导的裂解复合物处的 DNA 碱基对的潜在堆积和水溶性。最大限度地减少化合物的肝脏毒性。本研究的主轴是验证 hTop1 抑制活性作为一种可能的作用机制，并使用（异喹啉咪唑并喹唑啉）、（咪唑并喹唑啉）和（咪唑并异喹啉）。 DNA松弛测定鉴定出五种化合物作为hTop1抑制剂，分别属于咪唑异喹啉3a,b、咪唑并喹唑啉12和异喹啉咪唑并喹唑啉7a,b 。在针对不同癌细胞系的 MTT 细胞毒性测定中，化合物12对 HOS 骨癌细胞最有效（IC 50 = 1.47 μM）。与此同时，其他抑制剂没有检测到针对任何癌细胞类型的活性。化合物(12)在HOS癌细胞的3D多细胞肿瘤球体模型中表现出强大的穿透能力。对h
• SYNTHESIS OF 15<i>H</i>-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-<i>B</i>]QUINAZOLINE-7,13,15-TRIONES AND 14<i>H</i>-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-<i>B</i>]BENZO[<i>G</i>]QUINAZOLINE-8,14,16-TRIONE AS NEW POLYCYCLIC FUSED-RING SYSTEMS
  作者：Ahmed I. Khodair、Jean-Pierre Gesson、El-Sayed H. El-Ashry

  DOI：10.1080/104265090507533

  日期：2004.12.1

  3-Thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-dione (3) and 2-substituted-3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones(4a-l) were prepared from the reaction of 2-thioliydantoin. (2) and 3-substituted 2-thiohydantoin (5a-l) with 2-formyl benzoic acid (1). Alkylation of 3 under an anhydrous basic conditions afforded 4a-i. The alkylation of 3 in. aqueous basic solution, afforded 3-(alkyl-mercapto)imidazo[1,5-b]isoquinoline-1,5-diones (7a,b). Reactions of the aromatic amino acids 9a,b and 12 with 7a afforded 2-(2H-1,5dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)benzoic acids (10a,b) and 3-(2H-1,5-dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)-2-naphthalenecarboxylic acid (13), which were then cyclyzed by heating in acetic anhydride to afford 15H-isoquino[2',3':3,4]-imidazo[2,1-b]quinazoline-7,13,15-triones (11a,b) and 14H-isoquino[2',3':3,4]imidazo[2,1-b]benzo[g]quinazoline-8,14,16-trione (14). Some of the new compounds were tested for their antitumor activities.