. 2014 Oct 9;6(1):804–815. doi: 10.1039/c4sc02130d

Table 2. Structure–activity relationships for carbamide based HDAC inhibitors³⁰ .

			HDAC isoform inhibition IC₅₀ ^a (μM)			[Brain]/[plasma] and brain free fraction ^b (%)
Compound	R¹ group	R² group	HDAC1	HDAC2	HDAC3	[Brain]/[plasma] and brain free fraction ^b (%)
5			0.059 ± 0.015	0.261 ± 0.140	0.949 ± 0.034	nd

6			4.24 ± 0.257	3.13 ± 0.492	25.0 ± 1.71	nd

7			0.072 ± 0.029	0.086 ± 0.057	0.350 ± 0.018	nd

8			0.020 ± 0.003	0.131 ± 0.015	0.548 ± 0.162	nd

9			0.011 ± 0.005	0.095 ± 0.061	0.635 ± 0.308	nd

BRD2283			0.003 ± 0.002	0.054 ± 0.016	0.604 ± 0.039	nd

10			0.021 ± 0.005	0.079 ± 0.042	1.01 ± 0.16	nd

11			11.9 ± 1.17	13.23 ± 0.45	>33.33	nd

BRD3349			0.011 ± 0.003	0.049 ± 0.005	2.78 ± 0.02	0.04

BRD4884			0.029 ± 0.012	0.062 ± 0.031	1.09 ± 0.38	1.29
			Residence time T _1/2 (min)			1.29
			20	143	257	6%

12			2.36 ± 0.151	1.10 ± 0.019	>33.33	nd

^aValues are the mean of a minimum of two experiments. Data are shown as IC₅₀ values in μM ± standard deviation. Compounds were tested in duplicate in a 12-point dose curve with 3-fold serial dilution starting from 33.33 μM. nd = not determined.

^bBrain free fraction estimated based on brain tissue binding experiments.

Table 2. Structure–activity relationships for carbamide based HDAC inhibitors30 .

Table 2. Structure–activity relationships for carbamide based HDAC inhibitors³⁰ .