1147683-16-6Relevant articles and documents
Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR
Andrianov, Victor,Gailite, Vija,Lola, Daina,Loza, Einars,Semenikhina, Valentina,Kalvinsh, Ivars,Finn, Paul,Petersen, Kamille Dumong,Ritchie, James W.A.,Khan, Nagma,Tumber, Anthony,Collins, Laura S.,Vadlamudi, Sree M.,Bjoerkling, Fredrik,Sehested, Maxwell
experimental part, p. 1067 - 1085 (2009/08/14)
Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (nM) range against enzyme activity in HeLa cell extracts and sub-μM for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained).
