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Published on: June 23, 2019
1H-pyrazolo[2,3-d][1,2,4]triazine-3,7-diones as a new class of human leukocyte elastase inhibitors
P G Baraldi1, B Cacciari, R Romagnoli
1Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@dns.unife.it
Abstract:
A novel series of 1H-2-phenyl-substituted-pyrazolo[2,3-d][1,2,4]triazine-3,7-diones (3a-g) as potential inhibitors of Human Leukocyte Elastase (HLE) are reported, the acyl-pyrazole being probably involved in the inhibition mechanism of the serino-protease enzymes. The most potent inhibitor both in vivo and in vitro was 2-o-methoxyphenyl-5-methyl-6-nitro-pyrazolo[2,3-d][1,2,4]triazine-3,7-di one (3e), which significantly suppressed the HLE-induced pulmonary injury in rats when administered orally (100 mg/kg, 3 h prior to HLE administration.
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