Abstract
The discovery of a novel class of nitric oxide synthase (NOS) inhibitors, 2-substituted 1,2-dihydro-4-quinazolinamines, and the related 4'-aminospiro[piperidine-4,2'(1'H)-quinazolin]-4'-amines is described. Members of both series exhibit nanomolar potency and high selectivity for the inducible isoform of the enzyme (i-NOS) relative to the constitutive isoforms in vitro. Efficacy in acute and chronic animal models of inflammatory disease following oral administration has also been demonstrated using these compounds.
MeSH terms
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Acute Disease
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Administration, Oral
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Amines / chemical synthesis
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Amines / chemistry
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Amines / pharmacology
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Animals
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Arthritis, Experimental / drug therapy
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Cell Line
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Chronic Disease
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Injections, Intravenous
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Isoenzymes / antagonists & inhibitors
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type II
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Rats
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Spiro Compounds / chemical synthesis
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Structure-Activity Relationship
Substances
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Amines
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Enzyme Inhibitors
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Isoenzymes
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Quinazolines
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Spiro Compounds
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, rat