. Author manuscript; available in PMC: 2011 Jul 22.

Published in final edited form as: J Med Chem. 2010 Jul 22;53(14):5281–5289. doi: 10.1021/jm100499s

Table 1.

IC₅₀ values and decarbamoylation rates for thiadiazoles produced via Scheme 1.

Compound	IC₅₀^a (nM)	S.E.M.	decarbamoylation rate (min⁻¹)^b	S.E.M.
10	496	34	0.0007	0.0001
11	473	62	0.0037	0.0002
12	152	50	0.0010	0.0001
13	68	21	0.0030	0.0002
14	424	53	0.0016	0.0001
15	492	69	0.0043	0.0002
16	300	106	0.0013	0.0001
17	189	47	0.0042	0.0001

When appropriate, apparent IC₅₀'s for selected compounds against purified human LAL were determined by fitting (MATLAB, non-linear least squares trust-region algorithm) dose-response curves (obtained with the 4MUO assay) to the rectangular hyperbola y=m/(x+b)+c, for y=50, where y = normalized enzymatic activity [%] and x = compound concentration [nM], and m, b, c are coefficients. All fits had R² > 0.95. Data represent averages ± SEM of 3 independent experiments.

phLAL was incubated with 10 μM compound for 30 min, diluted 250× to 40 nM with substrate (0.125 mM). The reaction was monitored at 10 min intervals for 2 hours. The apparent decarbamoylation rates [min⁻¹] were calculated in MATLAB via linear regression of the plots of the equation described previously:¹⁶ ln(Fraction Inhibited) = −k*t, Fraction Inhibited = (Activity_DMSO-Activity_Compound)/Activity_DMSO for each time point. Data represent averages ± SEM of 4 independent experiments. R²>0.96 for all fits.