2,3-dihydro-3-hydroxymethylenethiopyrano[2,3-b]pyridin-4(4H)-one

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2,3-dihydro-3-hydroxymethylenethiopyrano[2,3-b]pyridin-4(4H)-one
• 英文别名: 3-(hydroxymethylidene)thiopyrano[2,3-b]pyridin-4-one
• 化学式: C₉H₇NO₂S
• 分子量: 193.226
• InChiKey: WBQJNERWQGEUJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.81
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.19
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-3-hydroxymethylenethiopyrano[2,3-b]pyridin-4(4H)-one 在 氯乙酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (Z)-3-(chloromethylene)-2H-thiopyrano[2,3-b]-pyridin-4(3H)-one
  参考文献：
  名称：

  PREPARATION AND APPLICATION OF NOVEL ANTIBACTERIAL AND ANTICANCER COMPOUNDS AND THEIR DERIVATIVES

  摘要：

  本发明揭示了化学式I、II、III、IV、衍生物、对映异构体、外消旋和非外消旋对映异构体混合物，或这些化合物的药学上可接受的盐或溶剂化物的新型抗生素和抗癌化合物。本发明还揭示了这些化合物的制备、制药组合物和生物活性。

  公开号：

  US20120035206A1
• 作为产物：
  描述：

  2,3-二氢吡喃并[2,3-b]吡啶-4(4H)-酮 、 甲酸乙酯 在 sodium hydride 、 水 作用下， 以 甲苯 为溶剂， 反应 10.0h， 生成 2,3-dihydro-3-hydroxymethylenethiopyrano[2,3-b]pyridin-4(4H)-one
  参考文献：
  名称：

  PREPARATION AND APPLICATION OF NOVEL ANTIBACTERIAL AND ANTICANCER COMPOUNDS AND THEIR DERIVATIVES

  摘要：

  本发明揭示了化学式I、II、III、IV、衍生物、对映异构体、外消旋和非外消旋对映异构体混合物，或这些化合物的药学上可接受的盐或溶剂化物的新型抗生素和抗癌化合物。本发明还揭示了这些化合物的制备、制药组合物和生物活性。

  公开号：

  US20120035206A1

文献信息

• Benzothiopyranoindole- and pyridothiopyranoindole-based antiproliferative agents targeting topoisomerases
  作者：Silvia Salerno、Valeria La Pietra、Mariafrancesca Hyeraci、Sabrina Taliani、Marco Robello、Elisabetta Barresi、Ciro Milite、Francesca Simorini、Aída Nelly García-Argáez、Luciana Marinelli、Ettore Novellino、Federico Da Settimo、Anna Maria Marini、Lisa Dalla Via

  DOI：10.1016/j.ejmech.2019.01.015

  日期：2019.3

  relaxation activity of both topoisomerases I and II, reasonably correlated to their intercalative capacities. Cleavable assay performed with topoisomerase I revealed a significant poisoning effect for compounds 5g, 5h, 5s, and 5t. A theoretical model provided by hydrated docking calculations clarified the role of the R1-R4 substituents on the topoisomerase I poison activity, revealing a crucial role of

  合成了新的苯并硫代吡喃并吲哚（5a-1）和吡啶并吡喃并吲哚（5m-t），它们在R 2 -R 4位和可质子化的R 1-二烷基氨基烷基链上具有不同的取代基组合（H，Cl，OCH 3），并通过三种方法进行了生物学分析。人肿瘤细胞系，显示出显着的抗增殖活性（GI 50值范围从0.31到6.93μM）和促凋亡作用。线性流二色性实验表明，遵循插入的结合模式，两种生色团与DNA形成分子复合物的能力。所有化合物均显示出适度的抑制拓扑异构酶I和II的松弛活性的能力，这与它们的嵌入能力合理相关。用拓扑异构酶I进行的裂解分析显示，化合物5g，5h，5s和5t具有明显的中毒作用。水合对接计算提供的理论模型阐明了R 1 -R 4的作用拓扑异构酶I上的取代基有毒活性，揭示了R 2 -OCH 3基团的关键作用。
• Synthesis of novel 1,4-dihydropyrido[3′,2′:5,6]thiopyrano[4,3-<i>c</i>]-pyrazoles and 5<i>H</i>-pyrido[3′,2′:5,6]thiopyrano[4,3-<i>d</i>]pyrimidines as potential antiproliferative agents
  作者：Giampaolo Primofiore、Anna Maria Marini、Federico Da Settimo、Silvia Salerno、Daniele Bertini、Lisa Dalla Via、Sebastiano Marciani Magno

  DOI：10.1002/jhet.5570400506

  日期：2003.9

  preparation of 2-substituted pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidines was accomplished from the intermediate 2,3-dihy-dro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL-60 and HeLa), but none of them showed any significant

  据报道，以具有取代的芳基的吡啶硫代吡喃并吡唑或吡啶硫吡喃并嘧啶核的存在为特征的新的平面衍生物的合成。通过2,3-二氢-3-羟基亚甲基硫代吡喃并[ 2,3- b ]吡啶的缩合反应，得到了新型的1,4-二氢吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]吡唑衍生物。-4（4 H）-ones与适当的肼。由中间体2,3-二氢-dro-3-二甲基氨基亚甲基硫代吡喃并[ 2,3- b ]制备2-取代的吡啶并[3'，2'：5,6]硫代吡喃并[4,3- d ]嘧啶。吡啶-4（4 H）-通过与适当的双亲核am反应而得到的。通过体外试验对人肿瘤细胞系（HL-60和HeLa）测试了某些新产品的抗增殖活性，但在所进行的测试中均未显示任何明显的作用。因此，线性流二色性测量表明它们不能与DNA形成分子复合物。
• Sulfonamides incorporating heteropolycyclic scaffolds show potent inhibitory action against carbonic anhydrase isoforms I, II, IX and XII
  作者：Elisabetta Barresi、Silvia Salerno、Anna Maria Marini、Sabrina Taliani、Concettina La Motta、Francesca Simorini、Federico Da Settimo、Daniela Vullo、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2016.01.018

  日期：2016.2

  Three series of polycyclic compounds possessing either primary sulfonamide or carboxylic acid moieties as zinc-binding groups were investigated as inhibitors of four physiologically relevant CA isoforms, the cytosolic hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides reported here showed excellent inhibitory effects against isoforms hCA II, IX and XII, but no highly

  研究了具有伯磺酰胺或羧酸部分作为锌结合基团的三个系列多环化合物作为四种生理相关的CA同工型（胞质hCA I和II，以及跨膜hCA IX和XII）的抑制剂。此处报道的大多数新磺酰胺类药物对hCA II，IX和XII亚型均表现出优异的抑制作用，但没有高度的亚型选择性抑制谱。在另一方面，羧酸盐选择性抑制HCA IX（ķ我小号测距40.8和92.7纳米之间）而不抑制显著其它同种型。结合了多环系统的磺酰胺/羧酸盐，例如苯并硫代吡喃并嘧啶，吡啶并硫代吡喃并嘧啶或二氢苯并噻吩并吡喃并[4,3- c]吡唑可能被认为是探索具有各种药理应用的异构体选择性CAI设计的有趣候选物。
• Synthesis and antiproliferative evaluation of new aryl substituted pyrido[3′,2′:5,6]thiopyrano[4,3-<i>c</i>]pyrazoles
  作者：G. Primofiore、A. M. Marini、S. Salerno、F. Da Settimo、D. Bertini、L. Dalla Via

  DOI：10.1002/jhet.5570420715

  日期：2005.11

  The preparation and the cytotoxic properties of new derivatives of the planar pyrido[3′,2′:5,6]thiopyrano-[4,3-c]pyrazole system, carrying an arylic side group in the 1 or 2 positions, are described. The novel substituted derivatives were obtained by reaction of suitable arylhydrazines with the appropriate key intermediate 3-hydroxymethylene-2,3-dihydrothiopyrano[2,3-b]pyridin-4(4H)-ones. Moreover

  描述了平面吡啶基[3'，2'：5,6]硫代吡喃基-[4,3- c ]吡唑系统的新衍生物的制备和细胞毒性，该衍生物在1或2位带有芳基侧基。通过使合适的芳基肼与合适的关键中间体3-羟基亚甲基-2，3-二氢硫代吡喃并[2，3- b ]吡啶-4-4 （4 H）-反应得到新的取代衍生物。此外，据报道制备了2-羧酰胺基苯基衍生物，其是通过与异氰酸苯酯反应从先前获得的吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]吡唑核完成的。通过体外评估所有新化合物的抗增殖能力 在人类肿瘤细胞系（HL-60和HeLa）上进行检测。
• Tricyclic Sulfonamides Incorporating Benzothiopyrano[4,3-<i>c</i>]pyrazole and Pyridothiopyrano[4,3-<i>c</i>]pyrazole Effectively Inhibit α- and β-Carbonic Anhydrase: X-ray Crystallography and Solution Investigations on 15 Isoforms
  作者：Anna M. Marini、Alfonso Maresca、Mayank Aggarwal、Elisabetta Orlandini、Susanna Nencetti、Federico Da Settimo、Silvia Salerno、Francesca Simorini、Concettina La Motta、Sabrina Taliani、Elisa Nuti、Andrea Scozzafava、Robert McKenna、Armando Rossello、Claudiu T. Supuran

  DOI：10.1021/jm300878g

  日期：2012.11.26

  Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous isozymes involved in crucial physiological and pathological events, representing the targets:, of inhibitors with several therapeutic applications. In this connection, we report a new class of carbonic anhydrase inhibitors, based on the thiopyrano-fused pyrazole scaffold to which a pendant 4-sulfamoylphenyl moiety was attached. The new sulfonamides 3a-e were designed as constrained analogues of celecoxib and valdecoxib. The most Interesting..,feature of sulfonamides 3 Was their predominantly strong inhibition of human (h) CA. I and II, as well as those of the rnycobacterial beta-class enzymes (Rv1284, Rv3273, and. Rv3588c), whereas their inhibitory action against hCA III, IV, VA, VB, VI, VII, IX, XII, XIII, and XIV was found to be at least 2 orders of magnitude lower. X-ray crystallography and structural superposition studies made it possible to explain the very distinct inhibition profile of the. tricyclic sulfonamides, different from thine of celecoxib and valdecoxib.