TY - JOUR
T1 - The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)
AU - Jagtap, P.
AU - Southan, G.J.
AU - Baloglu, E.
AU - Ram, E.
AU - Mabley, Jon
AU - Marton, A.
AU - Salzman, A.L.
AU - Szabo, C.
PY - 2004/1
Y1 - 2004/1
N2 - A series of novel 4-(N-acyl)-2,3-dihydro-1H-isoindol-1-ones have been prepared from methyl-3-nitro-2-methylbenzoate and linked through various spacers to the adenosine derivatives 11 and 12. We found that potent inhibition of poly(ADP-ribose)polymerase-1 (PARP-1) was achieved when isoindolinone was linked to adenosine by a spacer group of a specific length. Introduction of piperazine and succinyl linkers between the isoindolinone and adenosine core structures resulted in highly potent compounds 8a and 10b, which showed IC50 values of 45 and 100 nM, respectively.
AB - A series of novel 4-(N-acyl)-2,3-dihydro-1H-isoindol-1-ones have been prepared from methyl-3-nitro-2-methylbenzoate and linked through various spacers to the adenosine derivatives 11 and 12. We found that potent inhibition of poly(ADP-ribose)polymerase-1 (PARP-1) was achieved when isoindolinone was linked to adenosine by a spacer group of a specific length. Introduction of piperazine and succinyl linkers between the isoindolinone and adenosine core structures resulted in highly potent compounds 8a and 10b, which showed IC50 values of 45 and 100 nM, respectively.
U2 - 10.1016/j.bmcl.2003.10.007
DO - 10.1016/j.bmcl.2003.10.007
M3 - Article
SN - 0960-894X
VL - 14
SP - 81
EP - 85
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
ER -