The title compds. (I; Q = bond, CH2, NR5, O; X = CH, N; Y = bond, CH2, NR6; Z = CH, N; R1, R2 = H, alkyl; R3, R4 = H, halo, alkyl, alkoxy, haloalkyl, haloalkoxy; R5 = H, alkyl, COR7, Ph, PhCH2; R6 = H, alkyl, PhCH2; R7 = H, alkyl, Ph, PhCH2, OR8, NR9R10; R8 = alkyl; R9 = H, alkyl, Ph, PhCH2; R10 = H, alkyl, PhCH2), were prepd. Thus, 1-[3-(4-methylpiperazin-1-yl)phenyl]ethanone in EtOH was added over 2 h to a mixt. of tert-Bu (E)-3-(3-formylphenyl)acrylate and KOH in EtOH at -20° followed by stirring overnight at room temp. to give (E)-3-[3-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxopropenyl]phenyl]acrylic acid trifluoroacetate. The latter in DMF was stirred overnight with HOBT, EDC, Et3N, and H2NOTHP to give a product which was treated with HCl/Et2O overnight at room temp. to give (E)-N-hydroxy-3-[3-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxopropenyl]phenyl]acrylamide trifluoroacetate. This inhibited histone deacetylase with IC50 = 0.020 μM. [on SciFinder(R)]
Preparation of N-hydroxy piperazinylphenyloxopropenylphenylacrylamides and related compounds as histone deacetylase inhibitors / Minucci, Saverio; Pelicci, Pier Giuseppe; Mai, Antonello; Ballarini, Marco; Gargiulo, Gaetano; Massa, Silvio; Thaler, Florian; Pain, Gilles; Colombo, Andrea; Gagliardi, Stefania; Varasi, Mario; Mercurio, Ciro.. - (2004).
Preparation of N-hydroxy piperazinylphenyloxopropenylphenylacrylamides and related compounds as histone deacetylase inhibitors
Mai, Antonello;
2004
Abstract
The title compds. (I; Q = bond, CH2, NR5, O; X = CH, N; Y = bond, CH2, NR6; Z = CH, N; R1, R2 = H, alkyl; R3, R4 = H, halo, alkyl, alkoxy, haloalkyl, haloalkoxy; R5 = H, alkyl, COR7, Ph, PhCH2; R6 = H, alkyl, PhCH2; R7 = H, alkyl, Ph, PhCH2, OR8, NR9R10; R8 = alkyl; R9 = H, alkyl, Ph, PhCH2; R10 = H, alkyl, PhCH2), were prepd. Thus, 1-[3-(4-methylpiperazin-1-yl)phenyl]ethanone in EtOH was added over 2 h to a mixt. of tert-Bu (E)-3-(3-formylphenyl)acrylate and KOH in EtOH at -20° followed by stirring overnight at room temp. to give (E)-3-[3-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxopropenyl]phenyl]acrylic acid trifluoroacetate. The latter in DMF was stirred overnight with HOBT, EDC, Et3N, and H2NOTHP to give a product which was treated with HCl/Et2O overnight at room temp. to give (E)-N-hydroxy-3-[3-[(E)-3-[3-(4-methylpiperazin-1-yl)phenyl]-3-oxopropenyl]phenyl]acrylamide trifluoroacetate. This inhibited histone deacetylase with IC50 = 0.020 μM. [on SciFinder(R)]I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
