title: Optimization of a series of potent and selective ketone histone deacetylase inhibitors.
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.
authors.affiliation: IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. giovanna_pescatore@merck.com
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pescatore
authors.forename: Olaf
authors.initials: O
authors.lastname: Kinzel
authors.forename: Barbara
authors.initials: B
authors.lastname: Attenni
authors.forename: Ottavia
authors.initials: O
authors.lastname: Cecchetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fiore
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fonsi
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz-Fademrecht
authors.forename: Sergio
authors.initials: S
authors.lastname: Serafini
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
mesh_terms: D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007659:Ketones; D011994:Recombinant Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D015032:Zinc