W. Kemnitzer et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3045–3049
3049
tuting at the 2-position of the phenyl group with N,N-dimethyl-
amino or N,N-dimethylmethanamine led to potent compounds
with enhanced solubility properties. SAR studies also revealed that
substitution at the 2-position with a phenyl or pyrazolyl group re-
sulted in potent compounds. The amide linker was found to be
important for activity. Through SAR studies, compound 6s was
identified, which had sub-micromolar potency in both the caspase
activation assay and growth inhibition assay and was significantly
more soluble than 2a. Additional SAR studies via modifications of
other positions of the N-aryl-9-oxo-9H-fluorene ring will be re-
ported in future publications.
Entry
Sub
(%)
4
8
41
G1
(%)
78
32
29
S (%) G2M
(%)
1A
1B
1C
6
12
48
16
10
11
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Figure 1. Drug-induced apoptosis in HCT116 cells as measured by flow cytometric
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compound 2a for 48 h progressing to subG1.