TY - JOUR
T1 - Design and synthesis of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Part 3
T2 - In vitro evaluation of 1,3,4,5-Tetrahydro-benzo[c][1,6]- and [c][1,7]-naphthyridin-6-ones
AU - Ferraris, Dana
AU - Ficco, Rica Pargas
AU - Pahutski, Thomas
AU - Lautar, Susan
AU - Huang, Shirley
AU - Zhang, Jie
AU - Kalish, Vincent
PY - 2003/8/4
Y1 - 2003/8/4
N2 - The 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-napthyridin-6-ones are presented as a potent class of PARP-1 inhibitors. Derivatives of these partially saturated aza-5[H]-phenanthridin-6-ones were designed and synthesized with tertiary amines for salt formation, thus enhancing aqueous solubility, iv formulation and their potential use in acute ischemic injuries (i.e., myocardial ischemia and stroke). We found that partial saturation of the C-ring results in derivatives that are several times more potent than the aromatic C-ring derivatives. The general synthetic routes are presented herein as well as thorough in vitro potencies and SAR discussion for selected derivatives.
AB - The 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-napthyridin-6-ones are presented as a potent class of PARP-1 inhibitors. Derivatives of these partially saturated aza-5[H]-phenanthridin-6-ones were designed and synthesized with tertiary amines for salt formation, thus enhancing aqueous solubility, iv formulation and their potential use in acute ischemic injuries (i.e., myocardial ischemia and stroke). We found that partial saturation of the C-ring results in derivatives that are several times more potent than the aromatic C-ring derivatives. The general synthetic routes are presented herein as well as thorough in vitro potencies and SAR discussion for selected derivatives.
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U2 - 10.1016/S0960-894X(03)00465-7
DO - 10.1016/S0960-894X(03)00465-7
M3 - Article
C2 - 12852955
AN - SCOPUS:0037633723
VL - 13
SP - 2513
EP - 2518
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 15
ER -