Abstract
The synthesis and SAR development of a trisubstituted imidazole HDAC inhibitor is described. The compounds were synthesized with high diastereocontrol by leveraging Ellman sulfinyl imine chemistry. Structural elucidation provided insight into binding mode and supported design rational. Pharmacokinetic properties of lead compounds were determined.
Keywords:
HDAC; HIV; Latent reservoir; Medicinal chemistry; SAR analysis; X-ray structure.
Copyright © 2020 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / virology
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Crystallography, X-Ray
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HIV-1 / drug effects
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HIV-1 / physiology
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Histone Deacetylase Inhibitors / chemistry
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Histone Deacetylase Inhibitors / metabolism*
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Histone Deacetylase Inhibitors / pharmacology
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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism*
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Humans
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Imidazoles / chemistry
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Imidazoles / metabolism
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Imidazoles / pharmacology
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Inhibitory Concentration 50
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Rats
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Structure-Activity Relationship
Substances
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Histone Deacetylase Inhibitors
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Imidazoles
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Isoenzymes
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imidazole
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Histone Deacetylases