Kevan R. Thompson

Preparation and Cyclization of Aryloxyacetaldehyde Acetals; A General Synthesis of 2,3-Unsubstituted Benzofurans

Abstract An improved method for the preparation of 2,3-unsubstituted benzofurans is described. Specifically, the PPA catalysed cyclization of aryloxyacetaldehyde acetals to give (4–7)-substituted benzofurans has been achieved.

Prevention of human leukocyte elastase-mediated lung damage by 3-alkyl-4-azetidinones

Abstract Simple 3-alkyl-4-azetidinones have been previously reported as potent inhibitors of human leukocyte elastase (HLE). Further modification of these simple monocyclic β-lactams has led to development of substituted 4-azetidinones that both inhibit HLE in a time dependent manner and, like previously reported modified cephalosporin sulfones, prevent HLE-induced lung damage in hamsters.

Inhibition of human leukocyte elastase. 6. Inhibition by 6-substituted penicillin esters.

Abstract Penicillin amides substituted at C-6 with either an α- or β-trifluoroacetamido or an α-alkoxy functionality are reported as human leukocyte elastase (HLE) inhibitors. The structure activity relations for these derivatives are discussed and compared to the corresponding known cephalosporin structures in terms of chemical stability, HLE inhibition, and efficacy in an intratracheal (IT) lung hemorrhage assay.

The effect of N-acyl substituents on the stability of monocyclic β-lactam inhibitors of human leukocyte elastase

Abstract Substituted monocyclic β-lactam have recently been reported as inhibitors of human leukocyte elastase (HLE). Simple N-acetyl-2-azetidinone lead structures were found to undergo N-deacylation as well as β-lactam ring opening. The development of the N-carbamoyl-2-azetidinone nucleus was crucial to the stability of these compounds for effective oral bioavailability.