1.
Bioorg Med Chem Lett
; 20(1): 294-8, 2010 Jan 01.
Article
in English
| MEDLINE
| ID: mdl-19906529
ABSTRACT
Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.
Subject(s)
Antineoplastic Agents/chemistry , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylases/chemistry , Hydroxamic Acids/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Design , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/pharmacology , Mice , Mice, Nude , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Xenograft Model Antitumor Assays
2.
Eur J Med Chem
; 40(6): 597-606, 2005 Jun.
Article
in English
| MEDLINE
| ID: mdl-15922843
ABSTRACT
A series of pyrimidyl-5-hydroxamic acids was prepared for evaluation as inhibitors of histone deacetylase (HDAC). Amino-2-pyrimidinyl can be used as a linker to provide HDAC inhibitors of good enzymatic potency.
