Table 1.

Structures, IC₅₀s, and cLog D Values for COX-1 Inhibitors

Inhibitor	R1	R2	R3	clogD	IC50 (nM)a,b
					COX-1		COX-2
					Monkey	Human	Monkey	Human
4				2.76	40 ± 17	20 ±7	400 ±113	264 ±110
5	OMe	4-MeOC6H4	4-MeOC6H4	3.72	4.6 ± 1.3	5.0 ±5.2	> 1000	>1000
6	OCH2F	4-MeOC6H4	4-MeOC6H4	3.84	3.6 ± 1.0	4.0 ±2.0	>1000	841±102
7	SMe	4-MeOC6H4	4-MeOC6H4	4.01	10.0 ±0.5	1.0 ±3.6	n.d.c	>1000
8	SO2Me	4-MeOC6H4	4-MeOC6H4	2.99	11 ± 1	6.0 ±0.2	>1000	>1000
9	SOMe	4-MeOC6H4	4-MeOC6H4	2.88	3.6 ±1.8	2.0 ±0.9	n.d.	>1000
10	OMe	Ph	4-CNC6H4	3.62	n.d.	1.0 ± 1.4	200 ± 45	n.d.
11	CF3	4-MeOC6H4	4-MeOC6H4	3.72	5.0 ±3.0	3.0 ±3.2	n.d.	247 ±614
12	CF3	4-MeOC6H4	2-MeO-pyridin-5-yl	2.75	5.1 ± 1.5	4.0 ±5.9	125 ±34	>1000
13	CF3	2-MeO-pyridin-5-yl	4-MeOC6H4	2.74	n.d.	6.0 ±3.0	n.d.	776 ±71
14		4-MeOC6H4	4-MeOC6H4	3.71	125 ±2	42 ±8	n.d.	>1000
20	OCH2CF3	4-MeOC6H4	4-MeOC6H4	3.59	1.0 ±0.3	1.0 ±0.2	>1000	>1000
24	CF3	2-F-pyridin-5-yl	4-MeOC6H4	3.38	10 ± 3.0	2.0 ±0.1	n.d.	>1000
26	SCH2F	4-MeOC6H4	4-MeOC6H4	3.56	6.4 ± 0.8	5.0 ±3.9	n.d.	>1000
27	SOCH2F	4-MeOC6H4	4-MeOC6H4	2.33	5.0 ±2.0	3.0 ± 1.7	545 ±102	>1000
28	SO2CH2F	4-MeOC6H4	4-MeOC6H4	3.17	25 ±3	3.0 ±1.2	n.d.	>1000
31	OMe	Ph	4-MeOC6H4	3.76	3.0 ±2.5	3.00 ±0.06	n.d.	>1000
32	OCH2F	Ph	4-MeOC6H4	3.96	100	1.7 ±0.6	n.d.	100 ±25
34				2.80	>1000	>1000	1.0 ±0.5	1.0 ± 0.1

^aAll data are mean ± SD (n = 3).

^bCOX-1 rat whole blood IC₅₀s for 4, 5, 6, and 20, were 130, 418, 280, and 15 nM, respectively.

^cn.d. = not determined.