3-substituted nalidixic acid analog compound and its preparation method and uses in pharmacy

The technology of a kind of compound, naphthyridone, is applied in the application field in the preparation antitumor drug

Inactive Publication Date: 2006-02-15
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether the 3-position substitution of naphthyridone has corresponding characteristics has not been reported yet.

Method used

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  • 3-substituted nalidixic acid analog compound and its preparation method and uses in pharmacy
  • 3-substituted nalidixic acid analog compound and its preparation method and uses in pharmacy
  • 3-substituted nalidixic acid analog compound and its preparation method and uses in pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1: 1-ethyl-3-(2-benzoimidazolyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthalene Pyridine (1)

[0064]Enoxacin (3.19 g, 0.01 mol) and o-phenylenediamine (1.08 g, 0.01 mol) were mixed and ground in a mortar, added to the reaction bottle, 40 ml of polyphosphoric acid was added, and the air in the reaction bottle was removed under reduced pressure. When no bubbles are generated, feed nitrogen gas, stir slowly to 140°C and keep warm until the reaction solution is homogeneous, then raise the temperature to 180°C and react for 4 hours, then cool down to about 100°C, pour the reaction solution into 250 grams of crushed ice while stirring , set aside to cool, adjust the pH value to 9, filter with suction, and dry to obtain the crude product, recrystallize with DMF, and then use methanol-triethylamine as the developing solvent for column chromatography to obtain 0.90 g of off-white crystals, which are recrystallized with methanol. Column chromatography gave...

Embodiment 2

[0071] Example 2: 1-ethyl-3-(2-benzoxazolyl)-6-fluoro1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthalene Pyridine (2)

[0072] Using enoxacin and o-aminophenol as raw materials, the preparation method is the same as in Example 1, and recrystallized with DMF. Column chromatography gave a light yellow solid, yield 28.9%, mp233-5°C

[0073] IR(cm-1): 3412, 3289, 2981, 1637, 1473, 1445, 1265, 792

[0074] 1HNMR (δ, ppm, DMSO-d6):

[0075] 1.40(t, 3H, -CH3), 2.85(m, 4H, -CH2-*2), 3.67(d, 4H, -CH2-*2), 4.41(q, 2H, -CH2-), 7.37(m , 2H, 5`-H and 6`-H), 7.71(m, 2H, 4`-H and 7`-H), 7.98(d, 1H, 5-H), 8.93(s, 1H, 2- h)

[0076] Formula: C21H20N502F MW: 393.42

[0077] Anal (C%, H%, N%,) Calc: 64.11, 5.12, 17.80 Found: 63.76, 5.34, 17.97

[0078] MS(EI, m / s): 393(M+), 351(base peak)

Embodiment 3

[0080] 1-Ethyl-3-(2-benzothiazolyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine[1- Ethyl-3-(benzothiazol-2-yl)-6-fluro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine](IVf)

[0081] Using enoxacin and o-aminothiophenol as raw materials, the preparation method is the same as in Example 1, and recrystallized with methanol. Column chromatography gave a yellow solid, mp 257-9°C, yield 26.6%.

[0082] IR(cm-1): 3419, 1627, 1474, 1446, 1372, 1276, 792

[0083] 1HNMR (δ, ppm, DMSO-d6):

[0084] 1.44(t, 3H, -CH3), 2.87(m, 4H, -CH2-*2), 3.71(m, 4H, -CH2-*2), 4.53(q, 2H, -CH2-), 7.37(t , 1H, 5`-H), 7.50(t, 1H, 6`-H), 7.96(d, 1H, 7`-H), 8.07(m, 2H, 5-H and 4`-H), 9.24 (s, 1H, 2-H)

[0085] Formula: C21H20N50SF.H20 MW: 427.49

[0086] Anal (C%, H%, N%,) Calc: 59.00, 5.15, 16.38 Found: 58.08, 4.77, 16.26

[0087] MS (EI, m / s): 409 (M+), 367 (base peak).

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Abstract

Disclosed is a 3-substituted nalidixic acid analog compound and its preparation method and uses in pharmacy, wherein the compound has antineoplastic activity and a general formula (I) with the 3-position substituted by benzimidazole and benzothiazole, the preparation process of the compound comprises condensing various substituted naphthyridine ketone-3-formylic acid, o-phenylenediamine, o-aminophenol, o-aminobenzenethiol and into polyphosphoric acids. The compound can be used in preparing anti-cancer medicaments.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a new 3-position substituted naphthyridone compound, and also relates to a preparation method of the compound and an application thereof in preparing antitumor drugs. Background technique [0002] Quinolones have been used as antibacterial drugs for more than 30 years. They mainly exert antibacterial effects by inhibiting bacterial DNA topoisomerase, namely gyrase. But recently Wentland et al found that 3-quinolinone carboxylic acid derivative WIN57294 can also interact with mammalian TopII. Its EC was found in the DNA fragmentation test using Hela cell TopII 50 up to 7.6 μM. Moreover, the study also found that some 3-position non-carboxylic acid derivatives also have similar antitumor activity, such as the EC of 3-(2,6-dihydroxybenzyl) derivatives (WIN64593) 50 The value is 96 μM. In addition, the 7-position of quinolinone is substituted with other pyridine, 4-methyl-1-piperazinyl or p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/4375A61P35/00C07D221/00
Inventor 李志裕尤启冬郭青龙何训贵
Owner CHINA PHARM UNIV
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