6-(substituted phenoxy)-tetrazolo[5,1-a] phthalazine derivatives as antuepileptics and their pharmaceutically acceptable salts

A technology of chlorophenoxy and dichlorophenoxy is applied in the field of preparing antiepileptic drugs, and can solve problems such as side effects and discomfort

Active Publication Date: 2010-03-24
JILIN YINGLIAN SHANGDE SCI & TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these drugs all protect patients from various epileptic seizures to varying degrees, their side effects and discomfort prevent their use in long-term treatment

Method used

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  • 6-(substituted phenoxy)-tetrazolo[5,1-a] phthalazine derivatives as antuepileptics and their pharmaceutically acceptable salts
  • 6-(substituted phenoxy)-tetrazolo[5,1-a] phthalazine derivatives as antuepileptics and their pharmaceutically acceptable salts
  • 6-(substituted phenoxy)-tetrazolo[5,1-a] phthalazine derivatives as antuepileptics and their pharmaceutically acceptable salts

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0020] Preparation 1: 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine

[0021] To a mixture of 0.13 g (0.64 mmol) of compound II, 0.026 g of NaOH (0.64 mmol) and 0.64 mmol of p-chlorophenol, 25 mL of methanol was added, and the mixture was refluxed for about 4 hours. After the reaction, the solvent was distilled off, and the resulting residue was subjected to column chromatography (ethyl acetate:petroleum ether, 2:3) to obtain 6-(4-chlorophenoxy)-1,2,3,4-tetrazolium-[ 5,4-a]-2,3-Naphthyridine.

[0022] Melting point 199-201°C, yield 79.2%. 1 H-NMR (CDCl 3 , 300MHz) δ7.31-8.77(m, 8H, Ar-H).IR(KBr)cm -1 : 1035, 1243(C-O-C), 1618(C=N).MS m / z 298.5(M+1), 300.5(M+3).Anal.Calcd.for C 14 h 8 ClN 5 O: C 56.48, H 2.71, N 23.52. Found: C 56.52, H 2.73, N 23.46.

Embodiment A

[0023] Example A: Anticonvulsant Pharmacological Experiment and Neurotoxicity Experiment

[0024] All compounds provided herein were screened for their ability to prevent and treat chemically and electrically induced epilepsy in epilepsy. Maximal electroshock MES test, used to show the efficacy of antiepileptic drugs against generalized seizures. Convulsions were inhibited or prevented by administering the compound to the mice orally (P.O.).

[0025] A rotarod ataxia test was also performed on mice to evaluate the neurotoxicity of each of the proposed agents, and the TD 50 And the protection index PI. Using mice, the biological activity and neurotoxicity of the test compounds in the maximum electroshock (MES) test seizure threshold test were tested. See Krall, R.J.; Penry, J.K.; White, B.G.; Kupferberg, H.J.; Swinyard, E.A. Epilepsia. 1978, 19, 409.

[0026] Table 1. Results of anticonvulsant pharmacological experiments and neurotoxicity experiments (mg / kg, p.o)

[0027] ...

Embodiment B

[0028] Embodiment B: acute toxicity test

[0029] Compound 1 was administered orally and acute toxicity was evaluated. Animals were observed at regular intervals on the first day, and then daily for two consecutive weeks after treatment. The LD50 (the dose lethal to half of the animals) was assessed and the results showed that this Invention compound 1 has low toxicity, that is, LD50>7000mg / kg.

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Abstract

A compound represented by a general formula I, and salts formed by the addition reaction of the same and the pharmaceutically acceptable acids, wherein, R is selected from various halogenated alkanes.The compound represented by the general formula I and salts formed by the addition reaction of the same and the pharmaceutically acceptable acids, provided by the invention, can be used for treatingepilepsy.

Description

technical field [0001] The present invention relates to 6-(substituted phenoxy)-tetrazolo[5,1-a]phthalazine derivatives, their addition salts with pharmaceutically acceptable acids, their preparation methods and their use in the preparation of antiepileptic drugs and pharmaceutical compositions containing them. Background technique [0002] Epilepsy is a collective term used to describe a group of chronic convulsive disorders that are characterized by transient seizures accompanied by loss or disturbance of consciousness. A variety of antiepileptic drugs are available in clinical application, such as phenobarbital, phenytoin, carbamazepine, and valproic acid. Although these drugs protect patients from various epileptic convulsions to varying degrees, their side effects and discomfort prevent their use in long-term treatment. In order to improve the therapeutic effect and eliminate or reduce side effects, new compounds with new structural features and new mechanisms of acti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04A61K31/5025A61P25/08
Inventor 全哲山关丽萍孙先宇魏成喜张昌浩
Owner JILIN YINGLIAN SHANGDE SCI & TECH DEV
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