Substituted pyrazolone derivatives and their preparing process and pharmaceutical conpositions

A technology of compounds and medicinal salts, applied in the field of substituted pyrazolone derivatives and their preparation and pharmaceutical compositions, can solve the problem of hypoglycemia and side effects of sulfonylureas

Inactive Publication Date: 2005-03-16
CHINA PHARM UNIV
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Various biguanides and sulfonylureas have been used as therapeutic drugs for diabetes. However, biguanides have gastrointestinal reactions such as nausea, abdominal distension, diarrhea, and epigastric discomfort. Sulfonylureas have hypoglycemia side effects

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
  • Substituted pyrazolone derivatives and their preparing process and pharmaceutical conpositions
  • Substituted pyrazolone derivatives and their preparing process and pharmaceutical conpositions
  • Substituted pyrazolone derivatives and their preparing process and pharmaceutical conpositions

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0054] 3-Methyl-1-phenyl-4-[4-(5-methyl-2-phenyl-4-oxazolyl)methoxy]-benzylidene-2-pyrazoline-5- Preparation of ketones (1):

[0055] a. Preparation of 4-(5-methyl-2-phenyl-4-oxazolyl)methoxy-benzaldehyde (II): 5.50g (26.5mmol) 4-chloromethyl-5-methyl -2-Phenyl-oxazole (Compound IV, R 2 =R 3 =H. Refer to the literature Ber., 1915, 48: 897 and Chem. Pharm. Bull., 1971, 19(10): 2050. ), 3.23g (26.5mmol) of p-hydroxybenzaldehyde, 7.32g (53mmol) of potassium carbonate and 80ml of DMF were mixed, and stirred at 80°C for 3h. After cooling, water was added to dissolve unreacted potassium carbonate, and extraction was performed twice with ethyl acetate. The organic phases were combined, washed with water until neutral, and finally washed with saturated brine, and dried with anhydrous sodium sulfate. Concentrate to obtain crude product. The crude product was soaked in 2.5mol / L NaOH solution for 30min, filtered, washed with water until neutral, and dried under infrared light to obtain 7.51g...

example 2

[0062] 3-Methyl-1-phenyl-4-[4-(5-methyl-2-phenyl-4-oxazolyl)methoxy]-benzyl-2-pyrazoline-5-one( 2) Preparation: 1.2g (2.7mmol) of compound (I, R 1 =R 2 =R 3 =H) Dissolve in 20ml of dioxane, use 0.06g of 5% Pd / C as a catalyst, and stir with hydrogen at room temperature and pressure until no more hydrogen is absorbed. The reaction mixture was filtered, the catalyst was recovered, and the filtrate was concentrated and recrystallized from anhydrous methanol. After the crystals are completely precipitated, they are filtered, washed with a small amount of methanol, and dried under an infrared lamp to obtain 0.48 g of white solid, with a yield of 89.4%, mp 137-138°C.

[0063] IR(cm -1 ): 2922

[0064] ESI-MS: 452[M+H] + , 474[M+Na] + ;

[0065] Anal.C 28 H 25 N 3 O 3 Found(%) C74.25 H5.64 N9.03

[0066] Calcd(%)C74.48 H5.58 N9.31

example 3

[0068] 3-Methyl-1-phenyl-4-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolyl)methoxy]-benzylidene-2- Preparation of pyrazoline-5-one (3):

[0069] a. Preparation of 3-methoxy-4-(5-methyl-2-phenyl-4-oxazolyl) methoxy-benzaldehyde: refer to the preparation method of a in Reference Example 1 from 4-chloromethyl 5-methyl-2-phenyl-oxazole and vanillin prepared. The product is a light yellow solid, with a yield of 72.1%, mp 120-122°C.

[0070]b. Refer to the preparation method of Example 1b. The product is orange-red solid, with a yield of 78.8%, mp192~193°C.

[0071] IR(cm -1 ): 1675(C=O);

[0072] 1 HNMR(500Hz, CDCl 3 ), δ(ppm): 2.35(s, 3H, CH 3 ), 2.46(s, 3H, CH 3 ), 4.03(s, 3H, CH 3 ), 5.18(s, 2H, CH 2 ), 7.17 ~ 7.21 (m, 2H, Ar-H), 7.33 (s, 1H, CH), 7.39 ~ 7.46 (m, 5H, Ar-H), 7.69 ~ 7.72 (q, 1H, Ar-H), 7.94~7.97(d, 2H, Ar-H), 8.00~8.03(q, 2H, Ar-H), 9.01~9.02(d, 1H, Ar-H);

[0073] Anal.C 29 H 25 N 3 O 4 Found(%) C71.78 H5.10 N8.29

[0074] Calcd(%) C72.64 H5.25 N8.7...

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

Disclosed is a pyrazolone derivative having blood sugar lowering action represented by formula (I), wherein R1 is hydrogen or low level alkyl or low level alkoxy, R2, R3, R4, R5 are separate hydrogen atom, halogen, low level alkyl, low level alkoxy, hydroxy, cyano, methylmercapto or methylsulfuryl, L and M each represents a link formed by the combination of L and M.

Description

Technical field [0001] The present invention relates to a pyrazolone derivative substituted by an arylmethylene group (arylbenzyl) or a pharmaceutically acceptable salt thereof, a preparation method thereof and a pyrazolone derivative containing an arylmethylene group (arylbenzyl) substitution Pharmaceutical composition. Background technique [0002] Various biguanides and sulfonylurea compounds have been used as treatment drugs for diabetes. However, biguanides have gastrointestinal reactions such as nausea, bloating, diarrhea, upper abdominal discomfort and other side effects. Sulfonylureas have Hypoglycemia side effects. In this way, when using them, it is necessary to pay attention to preventive measures, and research on new treatments for diabetes hopes to have no such side effects. Takeda has developed a new class of compounds, 5-(4-alkoxybenzyl)-2,4-thiazolidinedione derivatives (Chem. Phar. Bull. 1982, 30, 3580-3600). These compounds can improve the sensitivity of tissues...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/427A61P3/10C07D263/32C07D413/12
Inventor 王亚楼刘星刘晓燕巫冠中
Owner CHINA PHARM UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap