Specificity, stability, and potency of monocyclic beta-lactam inhibitors of human leucocyte elastase.

Stable, potent, highly specific, time-dependent monocyclic β-lactam inhibitors of human leucocyte elastase (HLE) are described. The heavily substituted β-lactams are stable under physiological conditions including in the presence of enzymes of the digestive tract. The β-lactams were unstable in base. At pH 11.3 and 31 o C they were hydrolyzed with half-lives of 1.5-2 h. Hydrolysis produced characteristic products including the substituent originally at C-4 of the lactam ring, a substituted urea, and products resulting from decarboxylation of the acid after ring opening