Development of a selective HDAC inhibitor aimed at reactivating the HIV latent reservoir.

Authors :: Clausen DJ
Liu J
Yu W
Duffy JL
Chung CC
Myers RW
Klein DJ
Fells J
Holloway K
Wu J
Wu G
Howell BJ
Barnard RJO
Kozlowski J
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Sep 01; Vol. 30 (17), pp. 127367. Date of Electronic Publication: 2020 Jun 26.
Publication Year :: 2020
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.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Subjects :: Animals
CD4-Positive T-Lymphocytes virology
Crystallography, X-Ray
HIV-1 drug effects
HIV-1 physiology
Histone Deacetylase Inhibitors chemistry
Histone Deacetylase Inhibitors pharmacology
Histone Deacetylases chemistry
Humans
Imidazoles chemistry
Imidazoles metabolism
Imidazoles pharmacology
Inhibitory Concentration 50
Isoenzymes antagonists & inhibitors
Isoenzymes metabolism
Rats
Structure-Activity Relationship
Histone Deacetylase Inhibitors metabolism
Histone Deacetylases metabolism

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