1H-pyrazolo[2,3-d][1,2,4]triazine-3,7-diones as a new class of human leukocyte elastase inhibitors.
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.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@dns.unife.it
Cacciari
B
B
Romagnoli
R
R
Spalluto
G
G
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D013843:Thiazines; D019272:Leukocyte Elastase