Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F11%3A9744" target="_blank" >RIV/00216208:11110/11:9744 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/11:9744
Result on the web
<a href="http://dx.doi.org/10.1021/jm101071n" target="_blank" >http://dx.doi.org/10.1021/jm101071n</a>
DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase
Original language description
We report novel neuronal nitric oxide synthase (nNOS) inhibitors based on a symmetric double-headed aminopyridine scaffold. The inhibitors were designed from crystal structures of leads 1 and 2 (Delker, S. L.; Ji, H.; Li, H.; Jamal, J.; Fang, J.; Xue, F.; Silverman, R. B.; Poulos, T. L. Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of cerebral palsy. J. Am. Chem. Soc. 2010, 132, 5437-5442) and synthesized using a highly efficient route. The best inhibitor, 3j,showed low nanomolar inhibitory potency and modest isoform selectivity. It also exhibited enhanced membrane permeability. Inhibitor 3j binds to both the substrate site and the pterin site in nNOS but only to the substrate site in eNOS. These compounds provide a basis for further development of novel, potent, isoform selective, and bioavailable inhibitors for nNOS.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/1M0520" target="_blank" >1M0520: Center for Applied Genomics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
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Volume of the periodical
54
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
2039-2048
UT code for WoS article
000289215700006
EID of the result in the Scopus database
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