Synthesis and elastase inhibitory activity of 6 alpha-chloro-2,2-dimethyl-3 alpha-(pivaloyloxy)methylpenam sulfone, 6 alpha-chloro-2,2-dimethyl-3-exo-methylenepenam sulfone, benzyl and methyl 6 alpha-substituted penicillanate sulfones.
The triflates and pivalates of 3 alpha-hydroxymethyl-6-substituted-2,2-dimethylpenam sulfones 3, 5; methyl and benzyl 6-substituted penicillanates 6-9 and 3-exo-methylene-6-substituted-2,2-dimethylpenam sulfone 4 were synthesized. These novel compounds were evaluated as elastase inhibitors using porcine pancreatic elastase. The effects that structural modifications of substituents on C-3 and C-6 in the penam nucleus have on elastase activity were examined and several similarities and distinctions were identified when compared to the reported penicillin esters and amides elastase inhibitors.
Boschetti
C E
CE
Instituto de Química Orgánica de Síntesis (CONICET-UNR), Rosario, Argentina.
Mascaretti
O A
OA
Cricco
J A
JA
Roveri
O A
OA
D000818:Animals; D015394:Molecular Structure; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013407:Sulbactam / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology; D013552:Swine
D013450:Sulfones; D010196:Pancreatic Elastase; D013407:Sulbactam