4-(甲硫基)-2-氧代-6-苯基-1,2-二氢吡啶-3-腈 | 57663-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-(甲硫基)-2-氧代-6-苯基-1,2-二氢吡啶-3-腈
• 英文名称: 4-(methylthio)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile
• 英文别名: 3-cyano-4-methylthio-6-phenyl-2(1H)-pyridone；3-cyano-6-phenyl-4-methylthio-2H-pyridone；4-methylsulfanyl-2-oxo-6-phenyl-1,2-dihydro-pyridine-3-carbonitrile；3-Cyano-4-methylthio-6-phenyl-2(1H)-pyrridon；4-(Methylsulfanyl)-2-oxo-6-phenyl-1,2-dihydro-3-pyridinecarbonitrile；4-methylsulfanyl-2-oxo-6-phenyl-1H-pyridine-3-carbonitrile
• CAS: 57663-06-6
• 化学式: C₁₃H₁₀N₂OS
• 分子量: 242.301
• InChiKey: LMJDNUBVFKYAGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(甲硫基)-2-氧代-6-苯基-1,2-二氢吡啶-3-腈 在 三氯氧磷 作用下， 反应 20.0h， 以61.54%的产率得到2-chloro-3-cyano-6-phenyl-4-methylthiopyridine
  参考文献：
  名称：

  Saxena, Abhishek S.; Goel, Atul; Ram, Vishnu Ji, Journal of the Indian Chemical Society, 2003, vol. 80, # 4, p. 311 - 318

  摘要：

  DOI：
• 作为产物：
  描述：

  6-phenyl-3-cyano-4-methylsulfanyl-2H-pyran-2-one 在 尿素 作用下， 反应 0.25h， 以43%的产率得到4-(甲硫基)-2-氧代-6-苯基-1,2-二氢吡啶-3-腈
  参考文献：
  名称：

  Regioselective Syntheses of Functionalized 2-Aminopyridines and 2-Pyridinones through Nucleophile-Induced Ring Transformation Reactions

  摘要：

  通过不同的反应条件，利用尿素对6-芳基-3-氰基-4-甲基硫基-2H-吡喃-2-酮进行环转化，展示了一种高效的一锅法合成2-氨基-6-芳基-4-甲基硫基吡啶和6-芳基-3-氰基-4-甲基硫基-2(1H)-吡啶酮。采用多种溶剂和碱分别选择性地制备2-氨基吡啶或2-吡啶酮。在无溶剂条件下直接将2H-吡喃-2-酮与尿素熔融时，两个产品以1:1的比例获得，而在吡啶中加热回流反应则专门生成2-氨基吡啶，产率为80-90%。在150°C下，6-芳基-3-碳甲氧基-4-甲基硫基-2H-吡喃-2-酮与尿素反应生成的2-吡啶酮衍生物产率良好（70-80%）。

  DOI：

  10.1055/s-2005-862365

文献信息

• Synthesis and reactivity of 3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones: development of a novel kinase-focussed library
  作者：Lynette A. Smyth、Thomas P. Matthews、Peter N. Horton、Michael B. Hursthouse、Ian Collins

  DOI：10.1016/j.tet.2010.02.047

  日期：2010.4

  3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones and related 3-amino-2H-pyrazolo[4,3-c]pyridines were explored and adapted for parallel synthesis, resulting in a library of compounds suitable for screening against kinases and other cancer drug targets. Methods for substituent variation at five distinct positions around the bicyclic core were devised to generate sets of compounds containing two- or three-point

  3-氨基-1 H-吡唑并[4,3- c ]吡啶-4（5 H）-ones代表了一种潜在的有吸引力的杂芳骨架，用于药物发现化学。特别地，双环核心中氢键供体和受体基团的排列可以满足ATP竞争性结合激酶的要求。从简单的原料到新型功能化的3-氨基-1 H-吡唑并[4,3- c ]吡啶4-4 （5 H）-ones和相关的3-氨基-2 H-吡唑并[4,3- ]的高效和区域选择性途径C探索了吡啶并使其适于平行合成，从而形成了适合于针对激酶和其他抗癌药物靶标进行筛选的化合物文库。设计了在双环核周围五个不同位置取代基变化的方法，以生成包含两点或三点多样性的化合物。
• Theoretical interpretations of electronic and fluorescence spectra of new 2(1H)-pyridone derivatives in solution and solid state
  作者：Yasuhiro Shigemitsu、Masayori Hagimori、Naoko Mizuyama、Bo-Cheng Wang、Yoshinori Tominaga

  DOI：10.1016/j.dyepig.2013.07.024

  日期：2013.12

  properties of novel 2(1H)-pyridones. The compounds were found to be virtually non-fluorescence in solution while modestly fluorescent in solid state. The solvent effects on the UV–vis and fluorescence maxima were estimated by means of a series of ab-initio quantum chemical calculations in conjunction with Polarizable Continuum Model (PCM) method. Influence of structural displacements and intermolecular

  对新型2（1 H）-吡啶酮。发现该化合物在溶液中实际上是无荧光的，而在固态中则是适度的荧光。通过一系列从头算量子化学计算，结合可极化连续体模型（PCM），估算了溶剂对UV-vis和荧光最大值的影响。通过使用碎片分子轨道（FMO）方案，对两种代表性化合物的光谱进行了详细的研究，考察了晶体结构位移和分子间相互作用的影响。光谱的FMO对相互作用分析表明，（1）分子间氢键引起红移;（2）静电相互作用引起蓝移;（3）晶体堆积效应在真空中从最大值整体上引起了蓝移。
• Tominaga, Yoshinori; Kawabe, Masanori; Hosomi, Akira, Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1325 - 1331
  作者：Tominaga, Yoshinori、Kawabe, Masanori、Hosomi, Akira

  DOI：——

  日期：——
• Structure Guided Lead Generation for <i>M. tuberculosis</i> Thymidylate Kinase (Mtb TMK): Discovery of 3-Cyanopyridone and 1,6-Naphthyridin-2-one as Potent Inhibitors
  作者：Maruti Naik、Anandkumar Raichurkar、Balachandra S. Bandodkar、Begur V. Varun、Shantika Bhat、Rajesh Kalkhambkar、Kannan Murugan、Rani Menon、Jyothi Bhat、Beena Paul、Harini Iyer、Syeed Hussein、Julie A. Tucker、Martin Vogtherr、Kevin J. Embrey、Helen McMiken、Swati Prasad、Adrian Gill、Bheemarao G. Ugarkar、Janani Venkatraman、Jon Read、Manoranjan Panda

  DOI：10.1021/jm5012947

  日期：2015.1.22

  M. tuberculosis thymidylate kinase (Mtb TMK) has been shown in vitro to be an essential enzyme in DNA synthesis. In order to identify novel leads for Mtb TMK, we performed a high throughput biochemical screen and an NMR based fragment screen through which we discovered two novel classes of inhibitors, 3-cyanopyridones and 1,6-naphthyridin-2-ones, respectively. We describe three cyanopyridone subseries that arose during our hit to lead campaign, along with cocrystal structures of representatives with Mtb TMK. Structure aided optimization of the cyanopyridones led to single digit nanomolar inhibitors of Mtb TMK. Fragment based lead generation, augmented by crystal structures and the SAR from the cyanopyridones, enabled us to drive the potency of our 1,6-naphthyridin-2-one fragment hit from 500 mu M to 200 nM while simultaneously improving the ligand efficiency. Cyanopyridone derivatives containing sulfoxides and sulfones showed cellular activity against M. tuberculosis. To the best of our knowledge, these compounds are the first reports of non-thymidine-like inhibitors of Mtb TMK.
• TOMINAGA, YOSHINORI;KAWABE, MASANORI;HOSOMI, AKIRA, J. HETEROCYCL. CHEM., 24,(1987) N 5, 1325-1331
  作者：TOMINAGA, YOSHINORI、KAWABE, MASANORI、HOSOMI, AKIRA

  DOI：——

  日期：——