4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine | 1439401-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine
• 英文别名: (2,7-dimethyl-1,8-naphthyridin-4-yl)hydrazine
• CAS: 1439401-01-0
• 化学式: C₁₀H₁₂N₄
• 分子量: 188.232
• InChiKey: BHDNCVSQPUXLLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.53
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.83
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine 在 吡啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 4-(2,3,4,5-tetra-O-acetyl-D-xyloso)-2,7-dimethyl-1,8-naphthyridinyl hydrazone
  参考文献：
  名称：

  Synthesis, molecular docking of novel 1,8-naphthyridine derivatives and their cytotoxic activity against HepG2 cell lines

  摘要：

  A series of novel 2,7-dimethyl-1,8-naphthyridine derivatives substituted with Mannich bases 2a-d, N-beta-glycosides 6a-e, 7a-e, Schiff's bases 8a-c, pyrazolone 9, and S-alkylated derivatives 10a-c have been synthesized in good yields starting from 4-hydroxy-2,7-dimethyl-1,8-naphthyridine 1 through multi-step synthesis. The newly synthesized title compounds were evaluated for their HepG2 cell growth inhibition, the results revealed that all the tested compounds process inhibitory effects on the growth of HepG2 liver cancer cells. Compound 8b showed the highest inhibition activity against HepG2 cell line (IC50 equals 3.2 mu g/mL) among all tested compounds. The results were compared to 5-Fluorouracil (5-FU) and doxorubicin as reference drugs, (IC50 5 and 3.56 mu g/mL). Furthermore, molecular docking of compounds 3b, 6a, and 8b into the binding site of topoisomerase II was carried out. The results of the binding energy scores of these compounds were compared to the docking score of Vosaroxin, a known 1,8-naphthyridine derivative which is in clinical trials as potential anticancer drug. Compound 8b docking result revealed that it is the only tested compound that intercalate with DNA segment of the topoisomerase II, similar to Vosaroxin which was used as reference drug for docking comparison.

  DOI：

  10.1007/s00044-013-0604-6
• 作为产物：
  描述：

  4-氯-2,7-二甲基-1,8-二氮杂萘 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以80%的产率得到4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine
  参考文献：
  名称：

  Synthesis, molecular docking of novel 1,8-naphthyridine derivatives and their cytotoxic activity against HepG2 cell lines

  摘要：

  A series of novel 2,7-dimethyl-1,8-naphthyridine derivatives substituted with Mannich bases 2a-d, N-beta-glycosides 6a-e, 7a-e, Schiff's bases 8a-c, pyrazolone 9, and S-alkylated derivatives 10a-c have been synthesized in good yields starting from 4-hydroxy-2,7-dimethyl-1,8-naphthyridine 1 through multi-step synthesis. The newly synthesized title compounds were evaluated for their HepG2 cell growth inhibition, the results revealed that all the tested compounds process inhibitory effects on the growth of HepG2 liver cancer cells. Compound 8b showed the highest inhibition activity against HepG2 cell line (IC50 equals 3.2 mu g/mL) among all tested compounds. The results were compared to 5-Fluorouracil (5-FU) and doxorubicin as reference drugs, (IC50 5 and 3.56 mu g/mL). Furthermore, molecular docking of compounds 3b, 6a, and 8b into the binding site of topoisomerase II was carried out. The results of the binding energy scores of these compounds were compared to the docking score of Vosaroxin, a known 1,8-naphthyridine derivative which is in clinical trials as potential anticancer drug. Compound 8b docking result revealed that it is the only tested compound that intercalate with DNA segment of the topoisomerase II, similar to Vosaroxin which was used as reference drug for docking comparison.

  DOI：

  10.1007/s00044-013-0604-6

文献信息

• Synthesis and reactions of some novel 1-(2,7-dimethyl-1,8-naphthyridin-4-yl)hydrazine candidates
  作者：N. M. Khalifa、M. A. Al-Omar、N. S. Ahmed

  DOI：10.1134/s1070363217100292

  日期：2017.10

  A series of novel 1,8-naphthyridine derivatives containing Schiff bases and amino substituents were synthesized starting from the reaction of 4-hydrazinyl-2,7-dimethyl-1,8-naphthyridine with different active carbonyl groups, acid monoanhydrides and tetracarboxylic acid anhydrides. Structures of new compounds were elucidated by means of physical and spectroscopic analyses.

  从4-肼基-2,7-二甲基-1,8-萘啶与不同的活性羰基，酸性一酸酐和四羧酸酐反应开始，合成了一系列含有席夫碱和氨基取代基的新型1,8-萘啶衍生物。通过物理和光谱分析阐明了新化合物的结构。
• Substituted naphthyridinyl hydrazines as anti-liver cancer agents
  申请人：KING SAUD UNIVERSITY

  公开号：US09855255B1

  公开（公告）日：2018-01-02

  The substituted naphthyridinyl hydrazine compounds as anti-liver cancer agents are anti-liver cancer agents that inhibit proliferative pathways of cancer cells, thereby exhibiting potent in vitro and in vivo anticancer activity. The compounds have the formula: wherein R1 and R2 each are selected independently from hydrogen, mercapto, and C1-C5-alkyl, preferably methyl, ethyl, propyl, isopropyl or halogen; R3 and R4 each are selected independently from hydrogen, alkyl or halogen; and R5 is selected from substituted or unsubstituted aryl, more preferably from substituted phenyl, naphthyl, and substituted or unsubstituted heteroaryl, more preferably from furyl, pyrrolyl, thienyl, imidazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, benzothiazolyl, oxadiazolyl or sugar moities. These agents exert their action through topoisomerase II inhibition.

  被替代的萘啶基肼化合物作为抗肝癌药物，是能够抑制癌细胞增殖途径，从而表现出强大的体外和体内抗癌活性的抗肝癌药物。该化合物的化学式为：其中R1和R2各自独立地选择氢、巯基和C1-C5烷基，优选甲基、乙基、丙基、异丙基或卤素；R3和R4各自独立地选择氢、烷基或卤素；R5从取代或未取代的芳基中选择，更优选取代苯基、萘基和取代或未取代的杂环芳基，更优选呋喃基、吡咯基、噻吩基、咪唑基、噻二唑基、吡啶基、吡嗪基、嘧啶基、苯并噻唑基、噁唑基或糖基。这些药剂通过拓扑异构酶II抑制发挥作用。
• NAPHTHYRIDINYL HYDRAZINE DERIVATIVES AS POTENT PERIPHERAL ANALGESIC AGENTS
  申请人：KING SAUD UNIVERSITY

  公开号：US20180362524A1

  公开（公告）日：2018-12-20

  The naphthyridinyl hydrazine derivatives as potent peripheral analgesic agents are (E)-2-(substituted benzylidene)-1-(2,7-dialkyl-1,8-naphthyridinyl) hydrazines that provide effective peripheral analgesic activity, as demonstrated using the mouse writhing test. The new target compounds include at least one compound that demonstrates higher potency in providing analgesic relief in mice (Protection (%)=81.44) compared to the reference drug acetyl salicylic acid (Protection (%)=78.47). These results demonstrated that the target compound exerts acute analgesic action, suggesting that it may represent an alternative in the development of new therapeutic strategies. Preferably, the (E)-2-(substituted benzylidene)-1-(2,7-dialkyl naphthyridinyl) hydrazine has the formula: wherein R 1 and R 2 are alkyl, R 3 is hydrogen, and R 4 is NO 2 .

  萘啶基腙衍生物作为有效的周围镇痛剂，是(E)-2-(取代苯甲醛基)-1-(2,7-二烷基-1,8-萘啶基)腙类化合物，通过小鼠扭动试验表明具有有效的周围镇痛活性。新的目标化合物中至少有一种化合物在小鼠中提供更高效的镇痛缓解作用（保护率（%）=81.44），相比参考药物乙酰水杨酸（保护率（%）=78.47）。这些结果表明目标化合物具有急性镇痛作用，暗示它可能代表新治疗策略的一种替代选择。最好的情况是，(E)-2-(取代苯甲醛基)-1-(2,7-二烷基萘啶基)腙类化合物的化学式为：其中R1和R2为烷基，R3为氢，R4为NO2。