2-(4'-Fluorophenyl)-6-methyl-pyrido[1,2-a]pyrimidin-4-one | 191218-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(4'-Fluorophenyl)-6-methyl-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 2-(4-Fluorophenyl)-6-methylpyrido[1,2-a]pyrimidin-4-one
• CAS: 191218-45-8
• 化学式: C₁₅H₁₁FN₂O
• 分子量: 254.264
• InChiKey: VTSITKGXCCNYRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4'-Fluorophenyl)-6-methyl-pyrido[1,2-a]pyrimidin-4-one 在 diphenyl ether-biphenyl eutectic 作用下， 反应 4.0h， 以81%的产率得到2-(4-Fluoro-phenyl)-7-methyl-[1,8]naphthyridin-4-ol
  参考文献：
  名称：

  一类新型的高效和选择性A1腺苷拮抗剂：一系列1,8-萘啶衍生物的结构亲和力。

  摘要：

  合成了一系列在位置2带有苯基，在位置4和7带有多个取代基的1,8-萘啶衍生物（12-36），试图获得有效的，选择性的A1腺苷受体亚型拮抗剂。测试了这些化合物以评估它们与A2A和A3腺苷受体亚型相比对A1的亲和力。在牛脑皮质膜的结合研究中，大多数化合物显示出对低纳摩尔范围内的A1受体具有亲和力，而在亚纳摩尔范围内的两个对A1受体具有亲和力，并且具有相对于A2A和A3选择性的有趣程度。对4-取代的衍生物的比较表明，具有4-喹啉结构的4-OH取代引起A1和A2A亲和力的增加，并且通常还引起A1选择性的增加。7位上的取代类型可以极大地调节亲和力：在这个位置上最有趣的取代基似乎是吸电子基团。特别是7-氯萘啶25d表现出显着的选择性（A2A / A1比为670，A3 / A1比为14,000）与更高的A1亲和力（Ki = 0.15 nM）相关。对这些化合物12-36的NMR研究表明，被4-OH取代的化

  DOI：

  10.1021/jm990321p
• 作为产物：
  描述：

  4-氟苯乙酮 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 0.33h， 生成 2-(4'-Fluorophenyl)-6-methyl-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Antitumor Agents. 174. 2‘,3‘,4‘,5,6,7-Substituted 2-Phenyl-1,8-naphthyridin-4-ones:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization

  摘要：

  Two series of 2',3',4',5,6,7-substituted 8-phenyl-1,8-naphthyridin-4-ones and 2-phenylpyrido-[1,2-a]pyrimidin-4-ones have been synthesized and evaluated as cytotoxic compounds and as inhibitors of tubulin polymerization. Most 2-phenyl-1,8-naphthyridin-4-ones showed potent cytotoxic and antitubulin activities, whereas 2-phenylpyrido[1,2-a]pyrimidin-4-ones showed no activity in either assay. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization in the 2-phenyl-1,8-naphthyridin-4-one series. The 2-phenyl-1,8-naphthyridin-4-ones (44-49) with a methoxy group at the 3'-position showed potent cytotoxicity against most tumor cell lines with GI(50) values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen. Introduction of substituents (e.g. F, Cl, CH3, and OCH3) at the 4'-position led to compounds with reduced or little activity and substitution at the 2'-position resulted in inactive compounds. The effects of various A-ring substitutions on activity depend on the substitution in ring C. Compounds 44-50 were potent inhibitors of tubulin polymerization, with activity nearly comparable to that of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Compounds 44-49 also inhibited the binding of radiolabeled colchicine to tubulin, but the inhibition was less potent than that obtained with the natural products. Further investigation is underway to determine if substitution at the 3'-position and multisubstitutions in ring C will result in compounds with increased activity.

  DOI：

  10.1021/jm960858s

文献信息

• Condensation of substituted 2-aminopyridine with β-ketocarboxylic esters: 4<i>H</i>-pyrido[1,2-<i>a</i>]pyrimidin-4-ones and pyridin-2-ones
  作者：Pier Luigi Ferrarini、Claudio Mori、Clementina Manera、Filippo Mori、Vincenzo Calderone、Enrica Martinotti

  DOI：10.1002/jhet.5570360502

  日期：1999.9

  We report the condensation of substituted 2-aminopyridines 5 with β-ketocarboxylic esters in polyphosphoric acid. In this reaction were obtained together with the target compounds, 4H-pyrido[1,2-a]pyrirnidin-4-ones 6 also the pyridin-2-ones 7. All the compounds 7 were tested for their calcium-antagonistic activity but failed to evoke any vasorelaxant response.

  我们报道了在多磷酸中β-酮羧酸酯与2-氨基吡啶5的缩合反应。在该反应中，与目标化合物一起获得了4 H-吡啶并[1,2- a ]嘧啶-4-酮6和吡啶-2-酮7。测试所有化合物7的钙拮抗活性，但未能引起任何血管舒张反应。
• US5994367A
  申请人：——

  公开号：US5994367A

  公开（公告）日：1999-11-30
• US6071930A
  申请人：——

  公开号：US6071930A

  公开（公告）日：2000-06-06
• Antitumor Agents. 174. 2‘,3‘,4‘,5,6,7-Substituted 2-Phenyl-1,8-naphthyridin-4-ones:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization
  作者：Ke Chen、Sheng-Chu Kuo、Ming-Chieh Hsieh、Anthony Mauger、Chii M. Lin、Ernest Hamel、Kuo-Hsiung Lee

  DOI：10.1021/jm960858s

  日期：1997.7.1

  Two series of 2',3',4',5,6,7-substituted 8-phenyl-1,8-naphthyridin-4-ones and 2-phenylpyrido-[1,2-a]pyrimidin-4-ones have been synthesized and evaluated as cytotoxic compounds and as inhibitors of tubulin polymerization. Most 2-phenyl-1,8-naphthyridin-4-ones showed potent cytotoxic and antitubulin activities, whereas 2-phenylpyrido[1,2-a]pyrimidin-4-ones showed no activity in either assay. In general, a good correlation was found between cytotoxicity and inhibition of tubulin polymerization in the 2-phenyl-1,8-naphthyridin-4-one series. The 2-phenyl-1,8-naphthyridin-4-ones (44-49) with a methoxy group at the 3'-position showed potent cytotoxicity against most tumor cell lines with GI(50) values in the low micromolar to nanomolar concentration range in the National Cancer Institute's 60 human tumor cell line in vitro screen. Introduction of substituents (e.g. F, Cl, CH3, and OCH3) at the 4'-position led to compounds with reduced or little activity and substitution at the 2'-position resulted in inactive compounds. The effects of various A-ring substitutions on activity depend on the substitution in ring C. Compounds 44-50 were potent inhibitors of tubulin polymerization, with activity nearly comparable to that of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. Compounds 44-49 also inhibited the binding of radiolabeled colchicine to tubulin, but the inhibition was less potent than that obtained with the natural products. Further investigation is underway to determine if substitution at the 3'-position and multisubstitutions in ring C will result in compounds with increased activity.
• A Novel Class of Highly Potent and Selective A₁ Adenosine Antagonists:  Structure−Affinity Profile of a Series of 1,8-Naphthyridine Derivatives
  作者：Pier Luigi Ferrarini、Claudio Mori、Clementina Manera、Adriano Martinelli、Filippo Mori、Giuseppe Saccomanni、Pier Luigi Barili、Laura Betti、Gino Giannaccini、Letizia Trincavelli、Antonio Lucacchini

  DOI：10.1021/jm990321p

  日期：2000.7.1

  A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical

  合成了一系列在位置2带有苯基，在位置4和7带有多个取代基的1,8-萘啶衍生物（12-36），试图获得有效的，选择性的A1腺苷受体亚型拮抗剂。测试了这些化合物以评估它们与A2A和A3腺苷受体亚型相比对A1的亲和力。在牛脑皮质膜的结合研究中，大多数化合物显示出对低纳摩尔范围内的A1受体具有亲和力，而在亚纳摩尔范围内的两个对A1受体具有亲和力，并且具有相对于A2A和A3选择性的有趣程度。对4-取代的衍生物的比较表明，具有4-喹啉结构的4-OH取代引起A1和A2A亲和力的增加，并且通常还引起A1选择性的增加。7位上的取代类型可以极大地调节亲和力：在这个位置上最有趣的取代基似乎是吸电子基团。特别是7-氯萘啶25d表现出显着的选择性（A2A / A1比为670，A3 / A1比为14,000）与更高的A1亲和力（Ki = 0.15 nM）相关。对这些化合物12-36的NMR研究表明，被4-OH取代的化