Synthesis and preliminary evaluation of antidiabetic activity of 4-(3-(4-bromophenyl)-3-oxo-1-arylpropylamino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide.
- Author:
Ying-xia ZHANG
1
;
Ju-fang YAN
;
Li FAN
;
Wei-yu ZHANG
;
Zu-wen ZHOU
;
Xin CHEN
;
Xiao-yan SU
;
Xue-mei TANG
;
Da-cheng YANG
Author Information
1. School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
- Publication Type:Journal Article
- MeSH:
Glycoside Hydrolase Inhibitors;
Humans;
Hypoglycemic Agents;
chemical synthesis;
chemistry;
pharmacology;
Molecular Structure;
Oxazoles;
chemistry;
Peroxisome Proliferator-Activated Receptors;
agonists;
Protein Tyrosine Phosphatase, Non-Receptor Type 1;
antagonists & inhibitors;
Response Elements;
Structure-Activity Relationship;
Sulfonamides;
chemistry;
Thiazolidinediones;
pharmacology
- From:
Acta Pharmaceutica Sinica
2009;44(11):1244-1251
- CountryChina
- Language:Chinese
-
Abstract:
Diabetes mellitus is a common metabolic disease with a high and growing prevalence affecting 4% of the population worldwide, the development of safe and effective therapeutic drug is the major thrust for chemists and pharmacists. To search for active antidiabetic lead compound, we designed and synthesized some novel beta-amino ketone derivatives containing sulfamethoxazole moiety directly through Mannich reaction of sulfamethoxazole, 4-bromoacetophenone and some aromatic aldehydes catalyzed by concentrated hydogen chloride or iodine in the solution of ethanol at 24-40 degrees C with convenient operation, mild reaction condition and satisfactory yield (32%-90%). Their chemical structures were characterized by 1H NMR, 13C NMR, MS and HR-MS. Biological activity tests showed that, in the range of low concentration (5-10 microg x mL(-1)), these title compounds to a certain degree possess protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and a-glucosidase inhibitory activity, moreover, some could activate peroxisome proliferator-activated receptor response element (PPRE) moderately. The PPRE agonist activities of seven compounds are almost 40% of that of Pioglitazone (the positive control), compound 12 shows the strongest activity (66.35%) among them. Thus, it was found that some of 4-(3-(4-bromophenyl)-3-oxo-1-arylpropylamino)-N-(5-methyl-isoxazol-3-yl) benzenesulfonamide containing sulfamethoxazole moiety exhibited antidiabetic activity for the first time.
