Abstract
The synthesis and diversification of a densely functionalized azetidine ring system to gain access to a wide variety of fused, bridged, and spirocyclic ring systems is described. The in vitro physicochemical and pharmacokinetic properties of representative library members are measured in order to evaluate the use of these scaffolds for the generation of lead-like molecules to be used in targeting the central nervous system. The solid-phase synthesis of a 1976-membered library of spirocyclic azetidines is also described.
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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Azetidines / blood
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Azetidines / chemical synthesis
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Azetidines / pharmacokinetics*
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Caco-2 Cells
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Cell Membrane Permeability / drug effects
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Central Nervous System / cytology
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Central Nervous System / drug effects*
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Endothelial Cells / drug effects
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Humans
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Mice
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Molecular Structure
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Small Molecule Libraries / chemical synthesis*
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Small Molecule Libraries / pharmacokinetics*
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Solubility
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Spiro Compounds / blood
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / pharmacokinetics*
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Stereoisomerism
Substances
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Azetidines
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Small Molecule Libraries
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Spiro Compounds
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azetidine