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Highly ligand efficient and selectiveN-2-(thioethyl)picolinamide histone deacetylase inhibitors inspired by the natural product psammaplin A

Highly ligand efficient and selectiveN-2-(thioethyl)picolinamide histone deacetylase inhibitors inspired by the natural product psammaplin A
Highly ligand efficient and selectiveN-2-(thioethyl)picolinamide histone deacetylase inhibitors inspired by the natural product psammaplin A
Novel picolinamide-based histone deacetylase (HDAC) inhibitors were developed, drawing inspiration from the natural product psammaplin?A. We found that the HDAC potency and isoform selectivity provided by the oxime unit of psammaplin?A could be reproduced by using carefully chosen heterocyclic frameworks. The resulting (hetero)aromatic amide based compounds displayed very high potency and isoform selectivity among the HDAC family, in addition to excellent ligand efficiency relative to previously reported HDAC inhibitors. In particular, the high HDAC1 isoform selectivity provided by the chloropyridine motif represents a valuable design criterion for the development of new lead compounds and chemical probes that target HDAC1.
1860-7179
149-156
Baud, Matthias
8752d519-3d33-43b6-9a77-ab731d410c2e
Haus, Patricia
b0229be7-ae1b-4843-b7ca-70a014b03fc9
Leiser, Thomas
0a989c0c-4a10-4fb3-95eb-e7f511229e14
Meyer-Almes, Franz-Josef
9f252633-80d9-4a9b-bcc7-96c0891a2dcf
Fuchter, Matthew J.
a98083c4-2a98-4844-8289-5468ec472801
Baud, Matthias
8752d519-3d33-43b6-9a77-ab731d410c2e
Haus, Patricia
b0229be7-ae1b-4843-b7ca-70a014b03fc9
Leiser, Thomas
0a989c0c-4a10-4fb3-95eb-e7f511229e14
Meyer-Almes, Franz-Josef
9f252633-80d9-4a9b-bcc7-96c0891a2dcf
Fuchter, Matthew J.
a98083c4-2a98-4844-8289-5468ec472801

Baud, Matthias, Haus, Patricia, Leiser, Thomas, Meyer-Almes, Franz-Josef and Fuchter, Matthew J. (2012) Highly ligand efficient and selectiveN-2-(thioethyl)picolinamide histone deacetylase inhibitors inspired by the natural product psammaplin A. ChemMedChem, 8 (1), 149-156. (doi:10.1002/cmdc.201200450). (PMID:23184734 )

Record type: Article

Abstract

Novel picolinamide-based histone deacetylase (HDAC) inhibitors were developed, drawing inspiration from the natural product psammaplin?A. We found that the HDAC potency and isoform selectivity provided by the oxime unit of psammaplin?A could be reproduced by using carefully chosen heterocyclic frameworks. The resulting (hetero)aromatic amide based compounds displayed very high potency and isoform selectivity among the HDAC family, in addition to excellent ligand efficiency relative to previously reported HDAC inhibitors. In particular, the high HDAC1 isoform selectivity provided by the chloropyridine motif represents a valuable design criterion for the development of new lead compounds and chemical probes that target HDAC1.

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More information

Accepted/In Press date: 31 October 2012
e-pub ahead of print date: 26 November 2012
Published date: 23 December 2012

Identifiers

Local EPrints ID: 400515
URI: https://eprints.soton.ac.uk/id/eprint/400515
ISSN: 1860-7179
PURE UUID: 0e2a2ab8-a51f-45bf-b2e0-95c47135100f
ORCID for Matthias Baud: ORCID iD orcid.org/0000-0003-3714-4350

Catalogue record

Date deposited: 16 Sep 2016 15:59
Last modified: 14 Jul 2018 00:28

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