Benzo[b]thiophene-based histone deacetylase inhibitors.
Benzo[b]thienyl hydroxamic acids, a novel class of histone deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the C5- and C6-positions of the benzo[b]thiophene core to characterize SAR and develop optimal inhibitors. It was determined that substitution at the C6-position of the benzo[b]thiophene core with a three-atom spacer yielded optimal HDAC1 inhibition and anti-proliferative activity in murine erythroleukemia (SC-9) cells.
Witter
David J
DJ
Merck Research Laboratories, Department of Drug Design & Optimization, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. David_Witter@merck.com
Belvedere
Sandro
S
Chen
Liqiang
L
Secrist
J Paul
JP
Mosley
Ralph T
RT
Miller
Thomas A
TA
D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D056572:Histone Deacetylase Inhibitors; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D013876:Thiophenes