- 5-benzamidoisoquinolin-1-ones and 5-(ω-Carboxyalkyl)isoquinolin-1- ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2)
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PARP-2 is a member of the poly(ADP-ribose) polymerase family, with some activities similar to those of PARP-1 but with other distinct roles. Two series of isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors of PARP-2, usin
- Sunderland, Peter T.,Woon, Esther C. Y.,Dhami, Archana,Bergin, Aoife B.,Mahon, Mary F.,Wood, Pauline J.,Jones, Louise A.,Tully, Sophie R.,Lloyd, Matthew D.,Thompson, Andrew S.,Javaid, Hashim,Martin, Niall M. B.,Threadgill, Michael D.
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supporting information; experimental part
p. 2049 - 2059
(2011/05/14)
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- Synthesis of 3-substituted benzamides and 5-substituted isoquinolin-1(2H)-ones and preliminary evaluation as inhibitors of poly(ADP-ribose)polymerase (PARP)
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Inhibitors of poly(ADP-ribose)polymerase (PARP) inhibit repair of damaged DNA and thus potentiate radiotherapy and chemotherapy of cancer. 3-Substituted benzamides and 5-substituted isoquinolin-1-ones have been synthesised and evaluated for inhibition of PARP. Reduction of 3-(bromoacetyl)benzamide, followed by treatment with base, gave RS-3-oxiranylbenzamide. Reduction of 3-(hydroxyacetyl)benzonitrile with bakers' yeast gave the R-diol which was converted to R-3-(1,2-dihydroxyethyl)benzamide. Similar reduction of 3-(acetoxyacetyl)benzonitrile led towards the S-diol which was converted to its cyclic acetonide. E-2-(2,6-Dicyanophenyl)-N,N-dimethylethenamine was formed by condensation of 2,6-dicyanotoluene with dimethylformamide dimethyl acetal (DMFDMA); cyclisation under acidic conditions afforded 5-cyanoisoquinolin-1-one. Heck coupling of 5-iodoisoquinolin-1-one with propenoic acid formed E-3-(1-oxoisoquinolin-5-yl)propenoic acid. 3-Oxiranylbenzamide, 5-bromoisoquinolin-1-one and 5-iodoisoquinolin-1-one were among the most potent inhibitors of PARP activity in a preliminary screen in vitro. Copyright (C) 1998 Elsevier Science Ltd.
- Watson, Corrine Y.,Whish, William J. D.,Threadgill, Michael D.
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p. 721 - 734
(2007/10/03)
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