Table 1.

Inhibition of LPS-induced TNF-α production in RAW 264.7 cells, cell viability and calculated lipophilicity of assayed compounds 9–14, 16–20 are shown. The anti-TNF-α properties of the analogs are compared with those of revlimid 3

Compd	TNF-α activity (30 μM) Control = 100%		Cell viability (30 μM) Control = 100%		C log D a	Fold to 1 anti-TNF-α activity b
	% Control	P value	% Control	P value
3	109 ± 10	0.4482	106 ± 3	0.1252	− 1.31	1
9	55 ± 3	< 0.001	103 ± 2	0.1555	+1.39	45
10	96 ± 1	0.0734	112 ± 1	< 0.0001	+0.65	4
11	79 ± 3	0.0087	102 ± 2	0.2028	− 1.66	21
12	63 ± 2	0.0184	94 ± 3	0.1488	− 0.72	37
13	88 ± 2	0.0571	98 ± 2	0.4333	− 0.48	12
14	52 ± 2	0.0009	82 ± 6	0.0427	+0.27	48
16	55 ± 4	0.0092	109 ± 3	0.0762	− 1.75	45
17	61 ± 5	0.0154	116 ± 2	0.0163	− 1.98	39
18	67 ± 5	0.0043	84 ± 2	0.0018	− 2.13	33
19	104 ± 3	0.4214	95 ± 5	0.5793	− 1.93	−4
20	96 ± 2	0.5184	96 ± 4	0.6212	− 2.04	4

Presented values are mean ± S.E.M. of n = 3 measurements. A Students t-test was used to assess for statistically significant changes; P<0.05 was considered significant.

^aC log D – calculated log D values were determined at pH 7.0 (CompuDrug, Pallas).

^bFold to thalidomide (1) anti-TNF-α activity was defined as (100 − TNF-α activity % Change of every compound)/(100 − TNF-α activity % Change contrasted with 1), TNF-α activity % control for thalidomide was equal to 99% of levels achieved in the presence of vehicle. The TNF-activity of compound 17 compares favorably with that of A10 in Ref. 6c.