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. Author manuscript; available in PMC: 2014 Apr 1.
Published in final edited form as: Bioorg Med Chem. 2013 Feb 1;21(7):1880–1897. doi: 10.1016/j.bmc.2013.01.046

Table 5.

Analogs of 12a with potentially reduced metabolic liability.

graphic file with name nihms442143u5.jpg
No. R1 R2 5 μM SK T/Ca 50 μM SK T/C SDa 50 μM Growth T/Cb MLM t1/2 (min)c
12a S-Et Allyl 0.10 ± 0.06 0.07 ± 0.02 0.73 ± 0.07 2.3
12l S-CH2CF3 Allyl 0.45 ± 0.19 0.22 ± 0.08 0.86 ± 0.07 4.8
12m S-Et Me 0.66 ± 0.20 0.20 ± 0.14 0.83 ± 0.15 1.7
14 (SO)Et Allyl 1.00 ± 0.13 0.51 ± 0.31 1.01 ± 0.05 2.8
15 (SO2)Et Allyl 0.83 ± 0.31 0.70 ± 0.13 1.03 ± 0.03 3.8
19b S-Et CF3CH2 0.78 ± 0.36 0.49 ± 0.17 1.01 ± 0.04 3.0
a

Ratio of A405 of SK-cleaved substrate in GAS culture treated with the indicated concentration of test compound divided by A405 of DMSO control (see Section 5.1.1). Values are the mean of at least three experiments ± standard deviation.

b

Ratio of OD (600 nm) for growth of GAS in the presence of test compound divided by DMSO control. Values are the mean of at least three experiments ± standard deviation.

c

Half-life of parent compound during incubation with mouse liver microsomes.