Table 3:

Inhibitory activity of linker modified analogs

Compound	Series	L	R	PDE4D7- S129D IC50 (nM)	PDE4B1- S133D IC50 (nM)	PDE4D7- S129(wt) IC50 (nM)	Ratio B/D	Ratio Basal/Activated
18	A	CH2	−CH2CONH2	8.6	137	810	16	94
19	A	NH	−CH2CONH2	42.1	136	1665	3	40
20	A	SO2	−CH2CONH2	475	3830	NTb	8	-
21	A	N(Me)	−CH2CONH2	733	3287	NTb	4	-
22	B	NH	−CH2CH2OH	1.1	57	149	52	135
23	B	CH2	−CH2CONH2	1.7	225	313	132	184
24	B	O	−CH2CH2OH	1.8	58	251	32	139
25	B	CH2	−CH2CH2OH	2	584	534	292	267
26	B	NH	−CH2CONH2	2.6	43	146	17	56
27	B	O	−CH2CONH2	35	953	2431	27	69

^aSee table 1 for assay definitions. See experimental section for methods and detailed synthetic procedures.

^bNT: Not tested