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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1998-2-19
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pubmed:abstractText |
A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 microM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2-iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:ConnorJ RJR,
pubmed-author:CurrieM GMG,
pubmed-author:FokK FKF,
pubmed-author:HagenT JTJ,
pubmed-author:HansenD WDWJr,
pubmed-author:JeromeG MGM,
pubmed-author:ManningP TPT,
pubmed-author:MetzSS,
pubmed-author:MooreW MWM,
pubmed-author:PitzeleB SBS,
pubmed-author:TjoengF SFS,
pubmed-author:TothM VMV,
pubmed-author:TrivediMM,
pubmed-author:WebberR KRK,
pubmed-author:ZupecM EME
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
96-101
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:9438025-Animals,
pubmed-meshheading:9438025-Cerebellum,
pubmed-meshheading:9438025-Endothelium, Vascular,
pubmed-meshheading:9438025-Enzyme Inhibitors,
pubmed-meshheading:9438025-Humans,
pubmed-meshheading:9438025-Imines,
pubmed-meshheading:9438025-Isoenzymes,
pubmed-meshheading:9438025-Kinetics,
pubmed-meshheading:9438025-Lipopolysaccharides,
pubmed-meshheading:9438025-Male,
pubmed-meshheading:9438025-Molecular Structure,
pubmed-meshheading:9438025-Neurons,
pubmed-meshheading:9438025-Nitrates,
pubmed-meshheading:9438025-Nitric Oxide Synthase,
pubmed-meshheading:9438025-Nitrites,
pubmed-meshheading:9438025-Piperidines,
pubmed-meshheading:9438025-Rats,
pubmed-meshheading:9438025-Rats, Inbred Lew,
pubmed-meshheading:9438025-Recombinant Proteins,
pubmed-meshheading:9438025-Structure-Activity Relationship
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pubmed:year |
1998
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pubmed:articleTitle |
Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.
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pubmed:affiliation |
Department of Discovery Medicinal Chemistry, G. D. Searle Research and Development, Monsanto Company, St. Louis, Missouri 63198, USA.
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pubmed:publicationType |
Journal Article
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