2-(4'-Methylphenyl)-8-methyl-pyrido[1,2-a]pyrimidin-4-one

• 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'-Methylphenyl)-8-methyl-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 8-Methyl-2-(4-methylphenyl)pyrido[1,2-a]pyrimidin-4-one
• 化学式: C₁₆H₁₄N₂O
• 分子量: 250.3
• InChiKey: AISGNDHUZFGAAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4'-Methylphenyl)-8-methyl-pyrido[1,2-a]pyrimidin-4-one 以 paraffin 为溶剂， 反应 2.0h， 生成 2-(4'-Methylphenyl)-5-methyl-1,8-naphthyridin-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
• 作为产物：
  描述：

  2-氨基-4-甲基吡啶 、 (4-甲基苯甲酰基)乙酸乙酯 生成 2-(4'-Methylphenyl)-8-methyl-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Method for treating tumors using 2-aryl-naphthyridin-4-ones

  摘要：

  本发明提供了化合物的结构式 I：##STR1## 其中 A 和 R.sub.1 -R.sub.8 如本文所定义。结构式 I 的化合物抑制微管的聚合并具有抗有丝分裂活性。结构式 I 的化合物可能对治疗牛皮癣、痛风、乳头状瘤、疣和各种肿瘤有用。

  公开号：

  US05994367A1

文献信息

• Method for treating tumors using 2-aryl-naphthyridin-4-ones
  申请人：The University of North Carolina at Chapel Hill

  公开号：US05994367A1

  公开（公告）日：1999-11-30

  The present invention provides compounds of Formula I: ##STR1## wherein A and R.sub.1 -R.sub.8 are defined herein. The compounds of Formula I inhibit the polymerization of tubulin and possess antimitotic activity. The compounds of Formula I may be useful for the treatment of psoriasis, gout, papiloma, warts, and a variety of tumors.

  本发明提供了化合物的结构式 I：##STR1## 其中 A 和 R.sub.1 -R.sub.8 如本文所定义。结构式 I 的化合物抑制微管的聚合并具有抗有丝分裂活性。结构式 I 的化合物可能对治疗牛皮癣、痛风、乳头状瘤、疣和各种肿瘤有用。
• 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.