期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 46, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2021.116344
关键词
Cyclooxygenase; Inflammation; Nonsteroidal anti-inflammatory drug; Coxib; Prostaglandin; Arachidonic acid
资金
- NSFC [21971098]
- CIFMS [2019-I2M-5-074]
- Fundamental Research Funds for the Central Universities [lzujbky-2016-60, lzujbky-2018-k9]
A novel class of molecules with a basic structure of pyrazole N-aryl sulfonate was designed and synthesized using a new pyrazole sulfonate synthetic method. Several compounds within this class showed excellent anti-inflammatory and analgesic activities, as well as selective COX-2 inhibitory properties. The LD50 of two compounds in mice were found to be greater than 2000 mg/kg in acute oral toxicity assays conducted in vivo.
Based on a new pyrazole sulfonate synthetic method, a novel class of molecules with a basic structure of pyrazole N-aryl sulfonate have been designed and synthesized. The interest in conducting intensive research stems from quite evident anti-inflammatory effects exhibited by the compounds in preliminary animal experiments. A series of compounds were synthesized by different substitutions of the R1, R2, and R3 groups. Within the series, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and phenyl 5-methyl-3-(4-(trifluoromethyl) phenyl)-1Hpyrazole-1-sulfonate exhibited excellent anti-inflammatory activity (% inhibition of auricular edemas = 27.0 and 35.9, respectively); the in vivo analgesic activity of phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate was confirmed to be effective (inhibition ratio of writhing = 50.7% and 48.5% separately), and compounds phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate , 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate were identified as selective COX-2 inhibitors (SI = 455, 10,497 and >189 severally). In Acute Oral Toxicity assays conducted in vivo, the lethal dose 50 (LD50) of 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate to mice was >2000 mg/kg
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