Phosphorous acid analogs of L-680,833, a potent monocyclic β-lactam inhibitor of human leukocyte elastase

Analogs of the monocyclic beta-lactam human leukocyte elastase (HLE) inhibitor L-680,833 in which the carboxyl group is replaced by phosphorous acid moieties were synthesized and found to be potent inhibitors of the enzyme (k(inact)/K-i in the range 217,000-1,326,000 M(-1)s(-1)). Cellular activity was demonstrated by inhibition of the generation of the N-terminal cleavage product A alpha-(1-21) from the A alpha chain of fibrinogen.