Unlock instant, AI-driven research and patent intelligence for your innovation.

1-substituted-1H-1,2,4-triazole-formamide derivatives, preparation and application thereof

A 1H-1, derivative technology, applied in the field of chemistry, can solve the problems of patient side effects, damage, ineffectiveness, etc.

Inactive Publication Date: 2012-10-17
ZHEJIANG UNIV
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, existing drugs are only effective for 60-70% of epilepsy patients, and about 20-30% of patients do not respond to existing treatments at all
In addition, existing drugs often cause patients to have many side effects, such as sedation and neuronal damage.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 1-substituted-1H-1,2,4-triazole-formamide derivatives, preparation and application thereof
  • 1-substituted-1H-1,2,4-triazole-formamide derivatives, preparation and application thereof
  • 1-substituted-1H-1,2,4-triazole-formamide derivatives, preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1, methyl-1-(2,6-difluorobenzyl)-1 H -1,2,4-triazole-5-carboxylate (Ⅲ a ) and methyl-1-(2,6-difluorobenzyl)-1 H -1,2,4-triazole-3-carboxylate (Ⅳ a )

[0021] Methyl-1 H -1,2,4-Triazole-3-carboxylate (128 mg, 1.0 mmol) was dissolved in N,N-dimethylformamide (2.4 mL), and sodium hydride (48 mg) was added at room temperature, stirred for 10 minutes, 2,6-difluorobenzyl chloride (162 mg, 1.0 mmol) was added and reacted at 70 °C for about 2 hours. Add water (15 mL) to quench the reaction, extract with ethyl acetate (15 mL×3), and dry the organic layer over anhydrous sodium sulfate. : 1) Carry out column chromatography separation, can obtain

[0022] ①Pale yellow solid 16.7 mg, yield 6%; melting point: 86.3-87.5 °C.

[0023] 1 H NMR (500 MHz, CDCl 3 ): 7.96 (s, 1H), 7.36 (m, 1H), 6.96 (t, 2H, J = 7.5 Hz), 5.96 (s, 2H), 4.06 (s, 3H); 13 C-NMR (125 MHz, CDCl 3 ): 162.74, 160.69, 158.61, 151.32, 144.54, 131.25, 111.92, 111.76, 111.32, 53.45, 42.38.

[0024] ...

Embodiment 2

[0027] Embodiment 2, methyl-1-(2-chlorobenzyl)-1 H -1,2,4-triazole-5-carboxylate (Ⅲ b ) and methyl-1-(2-chlorobenzyl)-1 H -1,2,4-triazole-3-carboxylate (Ⅳ b )

[0028] The operating process is the same as in Example 1, except that 2,6-difluorobenzyl chloride is replaced with 2-chlorobenzyl chloride to obtain

[0029] ①Pale yellow crystals, yield: 6%; melting point: 86.8-87.8 °C.

[0030] 1 H NMR (500 MHz, CDCl 3 ): 8.06 (s, 1H), 7.43 (d, 1H, J = 8 Hz), 7.29 (t, 1H, J = 6 Hz), 7.23 (t, 1H, J = 7.5 Hz), 6.87 (d, 1H, J= 6.5 Hz), 5.96 (s, 2H), 4.00 (s, 3H).

[0031] ②White solid, yield: 58%; melting point: 90.4-91.1 °C.

[0032] 1 H NMR (500 MHz, CDCl 3 ): 8.19 (s, 1H), 7.46 (d, 1H, J = 8 Hz), 7.36 (m, 1H), 7.32 (m, 2H), 5.55 (s, 2H), 4.00 (s, 3H).

[0033]

Embodiment 3

[0034] Example 3, methyl-1-((2-chloropyridine-3-substituted) methyl)-1 H -1,2,4-triazole-5-carboxylate (Ⅲ c ) and methyl-1-((2-chloropyridine-3-substituted) methyl)-1 H -1,2,4-triazole-3-carboxylate (Ⅳ c )

[0035] The operation process is the same as in Example 1, except that 2,6-difluorobenzyl chloride is replaced with 3-(bromomethyl)-2-chloropyridine to obtain

[0036] ①Pale yellow solid, yield: 22%; melting point: 87.0-88.1 °C.

[0037] 1 H NMR (500 MHz, CDCl 3 ): 8.39 (d, 1H, J = 7.5 Hz), 8.10 (s, 1H), 7.24 (m, 1H), 7.19 (m, 1H), 5.96 (s, 2H), 4.02 (s, 3H).

[0038] ②White solid, yield: 51%; melting point: 90.7-91.5 °C.

[0039] 1 H NMR (500 MHz, CDCl 3 ): 8.44 (d, 1H, J = 4.5 Hz), 8.34 (s, 1H), 7.63 (d, 1H, J = 8 Hz), 7.33 (t, 1H, J = 4.5 Hz), 5.57 (s, 2H), 4.02 (s, 3H).

[0040]

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides 1-substituted-1H-1,2,4-triazole-formamide derivatives. The substitution position of formamido is in 5- or 3- position of 1H-1,2,4-triazole, rufinamide is a lead compound, the parent nucleus 1,2,3-triazole is replaced by 1,2,4-triazole, the structure of the side chain formamide is maintained, different substituted aromatic (heterocyclic) rings replace 2,6-difluorobenzene structure, the type, number or position of the substituent group on a benzene ring is changed to obtain a series of 1-substituted-1H-1,2,4-triazole-5-formamide / 1-substituted-1H-1,2,4-triazole-3-formamide derivatives. Pharmaceutical activity screening experiments prove that the compounds have good anticonvulsant activity, and can be applied to preparation of anticonvulsant medicaments. The preparation method has reasonable design, simple steps and practicality; and the derivatives have the structural general formula in the specification.

Description

Technical field [0001] The invention is the field of chemistry, involving 1-replacement -1 H -1,2,4-triazozole-5-tetamide (or 3-methylide) derivatives and their preparation methods, as well as the application of compounds in preparing epilepsy drugs. Background technique [0002] Epilepsy is a type of syndrome caused by a variety of pathological processes of the brain.About two million people around the world are diagnosed with epilepsy, and epilepsy has become a problem of about 1%of the world's population.The existing drugs are only effective for 60 ~ 70%of patients with epilepsy, and about 20 to 30%of patients do not have effect on existing treatment.In addition, existing drugs often cause many side effects in patients, such as sedative and neuronal damage.Therefore, it is obsessed with higher safety, lower toxicity, and stronger effectiveness of patients with stronger treatment. [0003] Lulidam is a sodium ion channel inhibitor, which has a broad -spectrum effectiveness for ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D249/10A61K31/4196A61P25/08
Inventor 刘滔高燕萍胡永洲陈忠董晓武
Owner ZHEJIANG UNIV