Optimization of a series of potent and selective ketone histone deacetylase inhibitors

Giovanna Pescatore; Olaf Kinzel; Barbara Attenni; Ottavia Cecchetti; Fabrizio Fiore; Massimiliano Fonsi; Michael Rowley; Carsten Schultz-Fademrecht; Sergio Serafini; Christian Steinkühler; Philip Jones

doi:10.1016/j.bmcl.2008.09.003

Optimization of a series of potent and selective ketone histone deacetylase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5528-32. doi: 10.1016/j.bmcl.2008.09.003. Epub 2008 Sep 6.

Authors

Giovanna Pescatore¹, Olaf Kinzel, Barbara Attenni, Ottavia Cecchetti, Fabrizio Fiore, Massimiliano Fonsi, Michael Rowley, Carsten Schultz-Fademrecht, Sergio Serafini, Christian Steinkühler, Philip Jones

Affiliation

¹ IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. giovanna_pescatore@merck.com

PMID: 18809328
DOI: 10.1016/j.bmcl.2008.09.003

Abstract

Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in the clinic. Herein we describe the optimization of a series of ketone small molecule HDAC inhibitors leading to potent and selective class I HDAC inhibitors with good dog PK.

MeSH terms

Administration, Oral
Animals
Cell Proliferation
Dogs
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
HeLa Cells
Histone Deacetylase 1
Histone Deacetylase Inhibitors*
Histone Deacetylases / metabolism*
Humans
Inhibitory Concentration 50
Ketones / chemistry*
Models, Chemical
Rats
Recombinant Proteins / chemistry
Zinc / chemistry

Substances

Enzyme Inhibitors
Histone Deacetylase Inhibitors
Ketones
Recombinant Proteins
HDAC1 protein, human
Histone Deacetylase 1
Histone Deacetylases
Zinc