Description
SSR 69071 is a potent inhibitor of neutrophil elastase (Ki = 0.0168 nM for the human enzyme). It is selective for human neutrophil elastase over rat, mouse, and rabbit elastases (Kis = 3, 1.8, 58 nM, respectively). It inhibits human neutrophil elastase ex vivo in mouse bronchoalveolar lavage (BAL) fluid (ED50 = 10.5 mg/kg, p.o.). In vivo, SSR 69071 (2.8 mg/kg, p.o.) reduces acute lung hemorrhage induced by human neutrophil elastase in mice. It reduces carrageenan- and human neutrophil elastase-induced paw edema in rats (ED30s = 2.2 and 2.7 mg/kg, respectively). SSR 69071 also reduces cardiac infarct size when administered prior to ischemia or reperfusion in a rabbit model of ischemia-reperfusion injury.
Uses
SSR 69071 is a novel and orally active elastase inhibitor.
Definition
ChEBI: 6-methoxy-1,1-dioxo-2-[[4-oxo-9-[2-(1-piperidinyl)ethoxy]-2-pyrido[1,2-a]pyrimidinyl]oxymethyl]-4-propan-2-yl-1,2-benzothiazol-3-one is a pyridopyrimidine.
Biological Activity
Orally active, high affinity and potent inhibitor of human leukocyte elastase (HLE) (IC 50 = 3.9 nM). Displays species-selectivity (K i values are 0.017, 1.70, 3.01, 58 and > 100 nM? for human, mouse, rat, rabbit and porcine elastase respectively). In vivo, inhibits HLE-induced lung hemorrhage in mice (ID 50 = 2.8 mg/kg) and reduces infarct size in an acute model of coronary ischemia-reperfusion injury.
