About: Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://dx.doi.org/10.1021/jm101071n
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. 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. (en)
Title	Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase (en)
skos:prefLabel	Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase (en)
skos:notation	RIV/00064165:_____/11:9744!RIV12-MZ0-00064165
http://linked.open...avai/predkladatel	Všeobecná fakultní nemocnice v Praze
http://linked.open...avai/riv/aktivita	I P Z
http://linked.open...avai/riv/aktivity	I, P(1M0520), Z(MSM0021620806)
http://linked.open...iv/cisloPeriodika	7
http://linked.open...vai/riv/dodaniDat	2012
http://linked.open...aciTvurceVysledku	Martásek, Pavel
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Všeobecná fakultní nemocnice v Praze / (nerozlišená součást)
http://linked.open...dnocenehoVysledku	233730
http://linked.open...ai/riv/idVysledku	RIV/00064165:_____/11:9744
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	selective inhibitors; p-glycoprotein; messenger-rna; disease; brain; binding; design; model; nos (en)
http://linked.open.../riv/klicoveSlovo	design disease model messenger-rna nos p-glycoprotein selective inhibitors binding brain
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[D45AE5E84A6E]
http://linked.open...i/riv/nazevZdroje	Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Center for Applied Genomics
http://linked.open...UplatneniVysledku	2011
http://linked.open...v/svazekPeriodika	54
http://linked.open...iv/tvurceVysledku	Martásek, Pavel Delker, S. L. Li, H. Y. Roman, L. J. Silverman, R. B. Xue, F. T. Fang, J. G. Poulos, T. L.
http://linked.open...ain/vavai/riv/wos	000289215700006
http://linked.open...n/vavai/riv/zamer	Molekulární biologie a patologie buňky za normy a u vybraných klinicky závažných patologických procesů
issn	0022-2623
number of pages	10 (xsd:int)
is http://linked.open...avai/riv/vysledek of	Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase Symmetric Double-Headed Aminopyridines, a Novel Strategy for Potent and Membrane-Permeable Inhibitors of Neuronal Nitric Oxide Synthase

Faceted Search & Find service v1.16.118 as of Jun 21 2024

Alternative Linked Data Documents: ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3240 as of Jun 21 2024, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (126 GB total memory, 39 GB memory in use)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software