6-氟-2-硫代-2,3-二氢-4(1H)-喹唑啉酮 | 69661-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 6-氟-2-硫代-2,3-二氢-4(1H)-喹唑啉酮
• 英文名称: 6-fluoro-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
• 英文别名: 6-fluoro-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 69661-42-3
• 化学式: C₈H₅FN₂OS
• mdl: MFCD09041760
• 分子量: 196.205
• InChiKey: GHVBYTWFUWPYDX-UHFFFAOYSA-N

物化性质

• 熔点：
  322 °C(Solv: acetic acid (64-19-7))
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氟-2-硫代-2,3-二氢-4(1H)-喹唑啉酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.25h， 生成 (S)-5-(3-fluoro-4-(((6-fluoro-4-oxo-3,4-dihydroquinazolin-2-yl)thio)methyl)phenyl)-N-(3-methyl-1-(methylamino)-1-oxobutan-2-yl)furan-2-carboxamide
  参考文献：
  名称：

  Development of matrix metalloproteinase-13 inhibitors – A structure-activity/structure-property relationship study

  摘要：

  A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhibitor 2, compound 31 was identified which exhibited microsomal hal-flife higher than 20 min, kinetic solubility higher than 20 mu M, and a permeability coefficient greater than 20x10(-6) cm/s. Compound 31 also showed excellent in vivo PK properties after IV dosing (C-max = 56.8 mu M, T-1/2 (plasma)= 3.0 h, Cl = 0.23 mL/min/kg) and thus is a suitable candidate for in vivo efficacy studies in an OA animal model.

  DOI：

  10.1016/j.bmc.2018.08.020
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酸 在 氯化亚砜 作用下， 以 丙酮 为溶剂， 反应 3.0h， 生成 6-氟-2-硫代-2,3-二氢-4(1H)-喹唑啉酮
  参考文献：
  名称：

  4(3H)-喹唑啉酮支架截短侧耳素衍生物对耐甲氧西林金黄色葡萄球菌的抗菌活性评价

  摘要：

  日益增长的抗生素耐药性正在引发医疗保健危机，导致迫切需要新的抗生素来应对严重的医院和社区感染。截短侧耳素是一种具有中等抗菌活性的天然产物，其独特的结构引起了人们对对其支架进行修饰以获得先导化合物的巨大努力。在此，我们报道了一系列在C-14侧链上具有4( 3H )-喹唑啉酮或其类似物支架的新型截短侧耳素衍生物的合成，并研究了它们对金黄色葡萄球菌、表皮葡萄球菌以及革兰氏阴性菌的体外活性。 -阴性细菌（大肠杆菌和沙门氏菌肠亚种。肠白痢）。构效关系(SAR)研究表明,4( 3H )-喹唑啉酮苯环上的取代基对于提高抗菌活性的作用不如取代位置重要,而4(3H)-喹唑啉酮N-3位上的取代基对提高抗菌活性的作用并不重要。 H )-喹唑啉酮对疗效有很大影响。用其他环（吡啶、吡咯、噻吩或环戊基）取代4(3 H )-喹唑啉酮的苯部分也显示出很高的抗菌功效，这意味着苯环对于发挥强大的抗菌性能来说是可有可无的。体外

  DOI：

  10.1016/j.ejmech.2022.114960

文献信息

• 2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F₄₂₀)-Dependent Nitroreductase (Ddn)
  作者：Yanlin Jian、He Eun Forbes、Fabian Hulpia、Martijn D. P. Risseeuw、Guy Caljon、Hélène Munier-Lehmann、Helena I. M. Boshoff、Serge Van Calenbergh

  DOI：10.1021/acs.jmedchem.0c01374

  日期：2021.1.14

  substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure–activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction

  交换先前合成但尚未公开的 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4 的 2 和4位取代基、闭环和进一步优化导致鉴定出有效的抗结核药物 2-硫代喹唑啉酮26。结构-活性关系（SAR）研究表明，两个间硝基取代基在抗结核活性中发挥着至关重要的作用，而在喹唑啉酮核心上引入极性取代基可以减少牛血清白蛋白（BSA）的结合（ 63c，63d）。虽然大多数测试的喹唑啉酮类化合物没有表现出针对 MRC-5 的细胞毒性，但通过 Ames 测试发现最有效的化合物26具有诱变性。该类似物对结核分枝杆菌胸苷酸激酶（3-氰基吡啶酮的靶标，位于当前类似物的基础上）表现出中等的抑制效力，表明本发明的S-取代的硫代喹唑啉酮的全细胞抗分枝杆菌活性可能是由于调节替代或额外目标。观察到受辅因子 F 420生物合成 ( fbiC )、辅因子还原 ( fgd ) 或去氮黄素依赖性硝基还原酶活性
• [EN] QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF<br/>[FR] COMPOSÉS QUINAZOLINONES ET LEURS DÉRIVÉS
  申请人：AMGEN INC

  公开号：WO2014036022A1

  公开（公告）日：2014-03-06

  Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是坦克酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• Quinazolinone Compounds and Derivatives Thereof
  申请人：AMGEN INC.

  公开号：US20150225396A1

  公开（公告）日：2015-08-13

  Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是坦克酰酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• 2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and <i>Mycobacterium tuberculosis</i>: Structure–Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization
  作者：Dinakaran Murugesan、Peter C. Ray、Tracy Bayliss、Gareth A. Prosser、Justin R. Harrison、Kirsteen Green、Candice Soares de Melo、Tzu-Shean Feng、Leslie J. Street、Kelly Chibale、Digby F. Warner、Valerie Mizrahi、Ola Epemolu、Paul Scullion、Lucy Ellis、Jennifer Riley、Yoko Shishikura、Liam Ferguson、Maria Osuna-Cabello、Kevin D. Read、Simon R. Green、Dirk A. Lamprecht、Peter M. Finin、Adrie J. C. Steyn、Thomas R. Ioerger、Jim Sacchettini、Kyu Y. Rhee、Kriti Arora、Clifton E. Barry、Paul G. Wyatt、Helena I. M. Boshoff

  DOI：10.1021/acsinfecdis.7b00275

  日期：2018.6.8

  Mycobacterium tuberculosis (MTb) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure-activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies. The compounds were inactivated by glutathione-dependent adduct formation as well as quinazolinone oxidation in microsomes. Pharmacokinetic studies demonstrated modest bioavailability and compound exposures. Resistance to the compounds in MTb was conferred by promoter mutations in the alternative nonessential NDH-2 encoded by ndhA in MTb. Bioenergetic analyses revealed a decrease in oxygen consumption rates in response to inhibitor in cells in which membrane potential was uncoupled from ATP production, while inverted membrane vesicles showed mercapto-quinazolinone-dependent inhibition of ATP production when NADH was the electron donor to the respiratory chain. Enzyme kinetic studies further demonstrated noncompetitive inhibition, suggesting binding of this scaffold to an allosteric site. In summary, while the initial MTb SAR showed limited improvement in potency, these results, combined with structural information on the bacterial protein, will aid in the future discovery of new and improved NDH-2 inhibitors.
• SINGH V. K.; JOSHI K. C., J. INDIAN CHEM. SOC., 1978, 55, NO 9, 928-931
  作者：SINGH V. K.、 JOSHI K. C.

  DOI：——

  日期：——