Table 1. Inhibition of p38α and PBMC Cytokine Release by 5-Aryl-2-(phenylthio)-6H-pyrimido[1,6-b]pyridazin-6-ones.

compd	R1	R2	R3	R4	p38α IC50 (μM)a	PBMC IL-1β IC50b (μM)	PBMC TNFα IC50b (μM)
10	Cl	H	H	Cl	5	20	20
11	H	H	H	H	>20	NDc	ND
12	Me	H	H	H	4.4	3.5	9.7
13	OMe	H	H	H	12	2.8	>20
14	CF3	H	H	H	11	2.1	>20
15	Cl	H	H	H	4.1	5.0	19.9
16	H	H	H	F	>20	15	>20
17	H	H	H	OMe	>20	20	>20
18	H	H	Cl	Cl	>20	>20	>20
19	CF3	F	H	H	1.7	1.0	3.1
20	F	F	H	H	3.5	3.7	15.3
21	Cl	Cl	H	H	0.25	0.40	0.46

^aAssayed according to ref (22).

^bSee Supporting Information for assay details.

^cND = not determined.