1H-pyrazole-1-carboxamidines: new inhibitors of nitric oxide synthase.
1H-Pyrazole-1-carboxamidines were prepared as potential inhibitors of the three isozymes of nitric oxide synthase. All of the compounds were found to be competitive inhibitors of all three isoforms. The most selective compound prepared was 1H-pyrazole-N-(3-aminomethylanilino)-1-carboxamidine (14), which is 100-fold selective for nNOS over eNOS with a Ki value of 2 microM.
Lee
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Y
Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA.
Martásek
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P
Roman
L J
LJ
Silverman
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RB
D000578:Amidines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D051379:Mice; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D052247:Nitric Oxide Synthase Type II; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000578:Amidines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat