| Summary: | Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1<i>H</i>,3<i>H</i>)-diones and quinazoline-4(3<i>H</i>)-one guanidine derivatives. In the present work, novel <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mi>N</mi><mn>1</mn></msup></semantics></math></inline-formula>,<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mi>N</mi><mn>3</mn></msup></semantics></math></inline-formula>-bis-substituted quinazoline-2,4(1<i>H</i>,3<i>H</i>)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled. The most potent NHE-1 inhibitor <b>3a</b> also possesses antiplatelet and intraocular-pressure-reducing activity. Compound <b>4a</b> inhibits NO synthesis and IL-6 secretion in murine macrophages without immunotoxicity and alleviates neutrophil infiltration, edema, and tissue lesions in a model of LPS-induced acute lung injury. Hence, we considered quinazoline derivative <b>4a</b> as a potential agent for suppression of cytokine-mediated inflammatory response and acute lung injury.
|
|---|