1364524-19-5Relevant academic research and scientific papers
Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent
Vianello, Paola,Botrugno, Oronza A.,Cappa, Anna,Dal Zuffo, Roberto,Dessanti, Paola,Mai, Antonello,Marrocco, Biagina,Mattevi, Andrea,Meroni, Giuseppe,Minucci, Saverio,Stazi, Giulia,Thaler, Florian,Trifiró, Paolo,Valente, Sergio,Villa, Manuela,Varasi, Mario,Mercurio, Ciro
, p. 1501 - 1517 (2016)
We report the stereoselective synthesis and biological activity of a novel series of tranylcypromine (TCPA) derivatives (14a-k, 15, 16), potent inhibitors of KDM1A. The new compounds strongly inhibit the clonogenic potential of acute leukemia cell lines. In particular three molecules (14d, 14e, and 14g) showing selectivity versus MAO A and remarkably inhibiting colony formation in THP-1 human leukemia cells, were assessed in mouse for their preliminary pharmacokinetic. 14d and 14e were further tested in vivo in a murine acute promyelocytic leukemia model, resulting 14d the most effective. Its two enantiomers were synthesized: the (1S,2R) enantiomer 15 showed higher activity than its (1R,2S) analogue 16, in both biochemical and cellular assays. Compound 15 exhibited in vivo efficacy after oral administration, determining a 62% increased survival in mouse leukemia model with evidence of KDM1A inhibition. The biological profile of compound 15 supports its further investigation as a cancer therapeutic.
NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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Page/Page column 62, (2012/03/27)
A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar
