Abstract
We report an efficient synthetic route to chiral pyrrolidine inhibitors of neuronal nitric oxide synthase (nNOS) and crystal structures of the inhibitors bound to nNOS and to endothelial NOS. The new route enables versatile structure-activity relationship studies on the pyrrolidine-based scaffold, which can be beneficial for further development of nNOS inhibitors. The X-ray crystal structures of five new fluorine-containing inhibitors bound to nNOS provide insights into the effect of the fluorine atoms on binding.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Catalytic Domain
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Crystallography, X-Ray
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Models, Molecular
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Molecular Structure
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Nitric Oxide Synthase Type I / antagonists & inhibitors*
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Nitric Oxide Synthase Type I / chemistry
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Nitric Oxide Synthase Type III / chemistry
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Protein Binding
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Rats
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Pyrrolidines
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type III