Linked Life Data

18502134

Source:http://linkedlifedata.com/resource/pubmed/id/18502134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-6-5
pubmed:abstractText
A series of new 7-monosubstituted and 3,7-disubstituted indazoles have been prepared and evaluated as inhibitors of nitric oxide synthases (NOS). 1H-indazole-7-carbonitrile (6) was found equipotent to 7-nitro-1H-indazole (1) and demonstrated preference for constitutive NOS over inducible NOS. By contrast, 1H-indazole-7-carboxamide (8) was slightly less potent but demonstrated a surprising selectivity for the neuronal NOS. Further substitution of 6 by a Br-atom at carbon-3 of the heterocycle enhanced 10-fold the inhibitory effects. Inhibition of NO formation by 6 appeared to be competitive versus both substrate and the cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin (H(4)B). In close analogies with 1, compound 6 strongly inhibited the NADPH oxidase activity of nNOS and induced a spin state transition of the heme-Fe(III). Our results are explained with the help of the X-ray structures that identified key-features for binding of 1 at the active site of NOS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5962-73
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile.
pubmed:affiliation
Institut Lavoisier, CNRS UMR 8180, Université de Versailles, 45 Avenue des Etats Unis, 78035 Versailles cedex, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't