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4-methyl-1h-diaryl pyrromonazole derivative and medicament usage thereof

A technology of diarylpyrazoles and derivatives, which is applied in the directions of drug combinations, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve the problems of easy tolerance and addiction, restricted use and the like

Active Publication Date: 2007-10-31
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cannabis substances have multiple pharmacological effects such as analgesic, sedative, anticonvulsant, antiemetic, antiglaucoma, and antihypertensive, but they are prone to tolerance and addiction, which limits their use (R.K.Razden, Pharmacol.Rew. , 1986, 38, 75-149)

Method used

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  • 4-methyl-1h-diaryl pyrromonazole derivative and medicament usage thereof
  • 4-methyl-1h-diaryl pyrromonazole derivative and medicament usage thereof
  • 4-methyl-1h-diaryl pyrromonazole derivative and medicament usage thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-N-(2-9H-fluorenyl)-4-methyl-1H-pyrazole-3-methyl Preparation of amides.

[0060]

[0061] Step 1 Preparation of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl chloride.

[0062] Take 0.5g of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid, dissolve it in 10ml of toluene, add 0.29ml of thionyl chloride, Heat to reflux. After 4 hours, distill off the thionyl chloride and toluene, then add 10ml of toluene three times, and distill to obtain 0.4g of reddish-brown oil. Feed directly to the next step reaction.

[0063] Step 2 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-N-(2-9H-fluorenyl)-4-methyl-1H-pyrazole-3-carboxamide preparation.

[0064] The formyl chloride obtained in the previous step was dissolved in 4 ml of dichloromethane, slowly added dropwise to a solution of 0.23 g of 2-aminofluorene and 0.234 ml of triethylamine in 5 ml of dichloromethane at 0°C, and reac...

Embodiment 2

[0066] Example 2 N-(4-bromophenyl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide preparation.

[0067]

[0068] Refer to Example 1 for the preparation method of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl chloride.

[0069] The obtained formyl chloride was dissolved in 4ml of dichloromethane, slowly added dropwise to a solution of 0.215g of p-bromoaniline and 0.234ml of triethylamine in 5ml of dichloromethane at 0°C, and reacted at room temperature for 9 hours. Separation with petroleum ether: ethyl acetate = 2: 1 column chromatography to obtain 0.327 g of N-(4-bromophenyl)-1-(2,4-dichlorophenyl)-5-(4-chlorobenzene base)-4-methyl-1H-pyrazole-3-carboxamide, mp: 157.6-159.3°C, two-step total yield 46.58%,

[0070] 1 H-NMR (DMSO, δppm): 2.29 (s, 3H), 7.26 (dd, 2H), 7.47-7.51 (m, 5H), 7.79-7.83 (m, 4H), 10.35 (s, 1H). FAB-MS (m / e): 536.0 (M + ).

Embodiment 3

[0071] Example 3 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-N-(3-pyridyl)-1H-pyrazole-3-carboxamide preparation.

[0072]

[0073] Refer to Example 1 for the preparation method of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl chloride.

[0074] The obtained formyl chloride was dissolved in 4ml of dichloromethane, slowly added dropwise to a solution of 0.141g of p-bromoaniline and 0.234ml of triethylamine in 5ml of dichloromethane at 0°C, and reacted at room temperature for 6.5 hours. Using petroleum ether: ethyl acetate = 1:3 column chromatography to obtain 0.311g of 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-N- (3-pyridyl)-1H-pyrazole-3-carboxamide mp: 162.8-164.1°C, two-step total yield 51.86%,

[0075] 1 H-NMR (DMSO, δppm): 2.31 (s, 3H), 7.27-7.38 (m, 3H), 7.47 (d, 2H), 7.60 (dd, 1H), 7.80-7.84 (m, 2H), 8.22- 8.30(m, 2H), 8.98(d, 1H), 10.47(s, 1H).FAB-MS(m / e): 457.0(M + ).

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Abstract

The invention relates to 4-metyl group-1H-diaryl pyrazole derivant and therapy salt, preparing method and usages to cure obesity, improve memory and stop smoking with therapy compound as inhibitor of inner brain cannabine I type (CB1) receptor inhibitor.

Description

field of invention [0001] The present invention relates to 4-methyl-1H-diarylpyrazole derivatives of general formula I and pharmaceutically acceptable salts thereof, their preparation methods, pharmaceutical compositions containing them and compounds of general formula I as brain cannabinoid type I Use of (CB1) receptor inhibitors in treating diseases or symptoms related to CB1 receptors, such as obesity, improving memory, and smoking cessation. Background technique [0002] Cannabis is one of the earliest addictive substances recognized by humans. It has a medicinal history of about one thousand years. Its main active ingredient is Δ 9 -tetrahydrocannabinol (delta-9-tetrahydro-cannabinol, Δ 9 -THC). Cannabis substances have multiple pharmacological effects such as analgesic, sedative, anticonvulsant, antiemetic, antiglaucoma, and antihypertensive, but they are prone to tolerance and addiction, which limits their use (R.K.Razden, Pharmacol.Rew. , 1986, 38, 75-149). [00...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/14C07D401/12C07D407/12C07D403/12A61K31/415A61K31/496A61K31/4439A61P3/04A61P25/28A61P25/34
Inventor 李松刘梦佳郑志兵王莉莉
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A