672305-45-2Relevant academic research and scientific papers
Synthesis and evaluation of N1/C4-substituted β-lactams as PPE and HLE inhibitors
Gerard, Stephane,Galleni, Moreno,Dive, Georges,Marchand-Brynaert, Jacqueline
, p. 129 - 138 (2004)
4-(Alkylamino)carbonyl-1-(alkoxy)carbonyl-2-azetidinones (9-11) have been prepared in five steps from 4-(benzyloxy)carbonyl-1-(t-butyldimethyl)silyl-2- azetidinone (1). The β-lactam reactivity of 9 has been established by 1H NMR experiment. Compound 11 was a good reversible inhibitor of PPE and HLE. Based on theoretical design, series of 2-azetidinones (12-17) and 4-(alkoxy)carbonyl-2-azetidinones (18-21) bearing various carbonyl (ester, thiolester, amide) and thiocarbonyl (thioamide) functionalities at position N1 were similarly prepared. In the absence of C4-substituent, the compounds were inactive against elastases. On the other hand, 4-(benzyloxy)carbonyl-1- (ethylthioxy)carbonyl-2-azetidinone (19) and 4-(benzyloxy)carbonyl-1- (benzylamino)thiocarbonyl-2-azetidinone (21) were both good reversible inhibitors, but acting most probably via different mechanisms (enzymic processing of the exocyclic ester function or β-lactam ring opening).
