Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC(50) of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.

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M o d i f i c a t i o n o f 8 -B r o m o g u a n i n e v i a I t s N 9 -T e t r a h y d r o f u r a n y l D e r i v a t i v e Abstract: A simple and straightforward method for the introduction of some N-and O-protecting groups into 8-bromoguanine has been developed using 2-acetylamino-8-bromo-6-oxo-9-(tetrahydrofuran-2-yl)-purine as a key intermediate.

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A method for the selective introduction of the N2-(dimethylamino)methylene group into 8-thio-9-(2-hydroxyethoxymethyl)guanine (1) has been developed. The effect of the N2-amidine protection on the S-alkylation of 1 was studied.