Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors |
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| Authors: | Anthony R. Gangloff Jason Brown Ron de Jong Douglas R. Dougan Charles E. Grimshaw Mark Hixon Andy Jennings Ruhi Kamran Andre Kiryanov Shawn O’Connell Ewan Taylor Phong Vu |
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| Affiliation: | 1. Takeda California, 10410 Science Center Dr, San Diego, CA 92121, USA;2. Quanticel Pharmaceuticals, 9393 Towne Center Dr #110, San Diego, CA 92121, USA |
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| Abstract: | Structure based drug design of a series of novel 1,4-benzoxazin-3-one derived PARP-1 inhibitors are described. The synthesis, enzymatic & cellular activities and pharmacodynamic effects are described. Optimized analogs demonstrated inhibition of poly-ADP-ribosylation in SW620 tumor bearing nude mice through 24 h following a single dose. |
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| Keywords: | Poly(ADP-ribose)polymerase inhibitors PARP-1 Structure-based drug design 1,4-Benzoxazin-3-one Chemopotentiation |
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