Biomedical subjects

Steve Price

Publications and source records attributed to Steve Price.

3 recordsLinked to original sources

PubMed2006

Identification and optimisation of a series of substituted 5-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

Further investigation of a series of thienyl-based hydroxamic acids that included ADS100380 and ADS102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided compounds 5a-g, 7a, b, 9, and 13a. Compound 5b demonstrated improved potency, in vitro DMPK profile, and rat oral bioavailability, compared to ADS102550. Functionalisation of the pendent phenyl group of compounds 5b, 5e and 13a provided analogues that possessed excellent enzyme inhibition and anti-proliferative activity.

Animals↗

PubMed2006

Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

Optimisation of ADS100380, a sub-micromolar HDAC inhibitor identified using a virtual screening approach, led to a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids (6a-i), that possessed significant HDAC inhibitory activity. Subsequent functionalisation of the pendent phenyl group of compounds 6f and 6g provided analogues 6j-w with further enhanced enzyme and anti-proliferative activity. Compound 6j demonstrated efficacy in a mouse xenograft experiment.

Animals↗

PubMed2005

Solid-phase synthesis of N-formylhydroxylamines (reverse/retro-hydroxamates).

N-Formylhydroxylamines, also known as reverse- or retro-hydroxamates, have become of significant interest in the recent past as inhibitors of metalloenzymes. Although solution-phase synthetic routes to such compounds have been reported, these are often lengthy and involve purification at each stage. Herein, novel three-step solid-phase synthetic approaches are described that enable libraries of such compounds to be produced in a convergent and efficient manner using commercially available starting materials. [reaction: see text]

Combinatorial Chemistry Techniques↗