3-(Dimethylaminomethylene)-4-thiochromanone | 69362-22-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 3-(Dimethylaminomethylene)-4-thiochromanone
• 英文别名: 3-dimethylaminomethylen-2,3-dihydro-benzo[3',2':5,6]thiopyran-4(4H)-one；3,4-dihydro-2-(dimethylaminomethylene)-4-thia-1(2H)-naphthalenone；3-(dimethylaminomethylidene)thiochromen-4-one
• CAS: 69362-22-7
• 化学式: C₁₂H₁₃NOS
• 分子量: 219.307
• InChiKey: LGUSLGPCYVYNEI-UHFFFAOYSA-N

物化性质

• 熔点：
  96 °C(Solv: isopropanol (67-63-0))
• 沸点：
  350.5±42.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(Dimethylaminomethylene)-4-thiochromanone 在 copper(l) iodide 、 sodium ethanolate 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 24.0h， 生成 2-(3-trifluoromethylanilino)-5H-benzothiopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  在2-苯基氨基取代的苯并硫吡喃并[4,3- d ]嘧啶作为激酶抑制剂的结构-活性关系中的新见解

  摘要：

  通过阻断血管内皮生长因子受体（VEGFR）信号传导通路抑制血管生成已成为抗癌治疗中的一项既定方法。到目前为止，许多单克隆抗体和具有ATP竞争能力的小分子抑制剂已在临床上得到验证和认可。在这项研究中，通过合成和生物学评估具有不同取代方式的新化合物1-21，进一步细化了2-苯基氨基取代的苯并硫吡喃并[4,3- d ]嘧啶类激酶抑制剂之间的结构-活性关系（SAR）在苯基侧基上，在8位与H，OCH 3或Cl结合。大多数化合物显示出有前途的人激酶插入结构域受体（KDR）抑制谱，IC 50值在亚微摩尔/低微摩尔范围内，并且有望对人脐静脉内皮细胞（HUVEC）以及一组三种人肿瘤细胞系具有抗增殖活性。针对最有前途的化合物16评估了针对一组六个人类激酶的血管激酶选择性谱。最后，计算研究允许在分子水平上阐明具有KDR的化合物建立的相互作用模式，突出了关键的稳定阳离子π相互作用，从而为进一步设计新型抑制剂提供了基础。

  DOI：

  10.1016/j.ejmech.2018.03.013
• 作为产物：
  描述：

  3-苯硫基丙酸 在 硫酸 作用下， 反应 19.0h， 生成 3-(Dimethylaminomethylene)-4-thiochromanone
  参考文献：
  名称：

  新型5H-硫代色素[4,3-d]嘧啶的合成及其抗宫颈癌活性

  摘要：

  通过不同的光谱技术，如1H NMR，13C NMR，质量和元素分析，合成，纯化和表征了一系列新颖的5H-硫代色素[4,3-d]嘧啶衍生物。评价了这些新化合物对人宫颈细胞系HeLa的抗宫颈癌活性。发现它们是有效的抗宫颈癌药物，相对于阳性对照药物阿霉素，GI50值小于10μg/ mL。

  DOI：

  10.2174/1570178616666190705152116

文献信息

• 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。
• Fused polycyclic 2-aminopyrimidine derivatives
  申请人：Celltech R & D Limited

  公开号：US06599908B1

  公开（公告）日：2003-07-29

  Fused polycyclic 2-aminopyrimidines of formula (1): wherein Ar is an optionally substituted aromatic or heteroaromatic group; X is a carbon or nitrogen atom; Y is a carbon or nitrogen atom; Z is a linker group; A together with X and Y forms an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof are described. The compounds are potent and selective inhibitors of the protein tyrosine kinases p56lck and p59fyn and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate p56lck and/or p59fyn activity is believed to have a role.

  化合物的化学式为（1）：其中，Ar为可选取代的芳香或杂芳基；X为碳或氮原子；Y为碳或氮原子；Z为连接基；A与X和Y一起形成可选取代的单环或双环芳香或杂芳基；以及其盐、溶剂化物、水合物和N-氧化物。这些化合物是蛋白酪氨酸激酶p56lck和p59fyn的有效选择性抑制剂，并可用于预防和治疗免疫疾病、高增殖性疾病和其他与不适当的p56lck和/或p59fyn活性有关的疾病。
• Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity
  作者：Olga Bruno、Silvia Schenone、Angelo Ranise、Francesco Bondavalli、Walter Filippelli、Giuseppe Falcone、Giulia Motola、Filomena Mazzeo

  DOI：10.1016/s0014-827x(98)00109-8

  日期：1999.1

  A series of N-methyl-N-pyrimidin-2-yl glycines 2a-e, having the pyrimidine ring fused with a cyclohexane [N-methyl-N-(5,6,7,8-tetrahydroquinazolin-2-yl)glycine], cyclohexene [N-methyl-N-(5,6-dihydroquinazolin-2-yl)glycine], 1,2,3,4-tetrahydronaphthalene [N-methyl-N-(5,6-dihydrobenzo[e]quinazolin-2-yl)glycine], benzopyrane [N-methyl-N-(5-phenyl-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl)glyci ne] and benzothiopyrane [N-methyl-N-(5H-[1]benzothiopyrano[4,3-d]pyrimidin-2-yl)glycine] ring, was prepared and tested for antiinflammatory activity. With the same purpose a number of N-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl substituted amino acids 3a-e, having a different chain length and branching were also synthesized and tested. All the described products 2 and 3 showed an appreciable antiphlogistic activity, particularly 2b and 2c.
• Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d]pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2
  作者：Silvia Salerno、Anna Maria Marini、Giacomo Fornaciari、Francesca Simorini、Concettina La Motta、Sabrina Taliani、Stefania Sartini、Federico Da Settimo、Aída Nelly García-Argáez、Ornella Gia、Sandro Cosconati、Ettore Novellino、Pilar D'Ocon、Anna Fioravanti、Paola Orlandi、Guido Bocci、Lisa Dalla Via

  DOI：10.1016/j.ejmech.2015.08.027

  日期：2015.10

  Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' anti-proliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on recombinant human kinase insert domain receptor (KDR), by cell-based phospho-VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity profile of the best performing derivatives belonging to series 2 was further explored combining modeling studies and additional assays in a panel of human cell lines and other kinases. (C) 2015 Published by Elsevier Masson SAS.
• New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: synthesis and pharmacological screening
  作者：Olga Bruno、Silvia Schenone、Angelo Ranise、Francesco Bondavalli、Elisabetta Barocelli、Vigilio Ballabeni、Milena Chiavarini、Simona Bertoni、Massimiliano Tognolini、Mariannina Impicciatore

  DOI：10.1016/s0968-0896(00)00272-8

  日期：2001.3

  The preparation and the pharmacological screening of novel anti-aggregatory/antiphlogistic polycyclic pyrimidine derivatives are described. The compounds were developed starting from bioactive 2-aminobenzopyranopyrimidine derivatives in order to assess the importance of the benzopyrano[4,3-d]pyrimidine structure and the role of an amino basic moiety in position 2. Antiplatelet activity was assessed in vitro against ADP and arachidonic acid-induced aggregation in guinea-pig plasma. Anti-inflammatory analgesic/antipyretic activities were studied in rat paw oedema, mouse writhing test and E coli-induced rat fever. Ulcerogenic and gastroprotective effects were also investigated in vivo on rat gastric mucosa. Among the tested compounds, the 5-substituted benzopyranopyrimidine derivatives 3d and 4d proved to be the most active antiplatelet agents as potent as acetylsalicylic acid against arachidonic acid-stimulated aggregation. Furthermore the 2-methylthio derivative 4d was endowed with greater efficacy against ADP aggregation suggesting that additional non-TXA(2) dependent mechanisms are involved in its biological activity. Orally administered at 100 mg kg(-1) in rats this latter compound displayed antiphlogistic acitivity comparable to indomethacin (10 mg kg(-1)) coupled with an unusual gastroprotective effect on ethanol-induced ulcers. In conclusion, these findings indicate that the 5-pyrrolidino-2-methylthiobenzopyrano[4d] fulfils the chemical requirements to exhibit antiplatelet activity associated with gastroprotective effect. (C) 2001 Elsevier Science Ltd. All rights reserved.