Table 1:

Inhibitory activity of triazine Ar1 substitution

Compound	R	PDE4D7- S129D IC50 (nM)a	PDE4B1- S133D IC50 (nM)b	PDE4D7- S129(wt) IC50 (nM)c	Ratio B/Dd	Ratio Basal/Activatede
4	−(CH2)3-OH	0.2	11	27	55	135
5	−CH2CH2OH	0.5	24	102	48	204
6	−CH2CONH2	5	48	203	10	41
7	−CH2OH	12	105	351	9	30
8	−CONH2	22	44	252	2	11
9	−CH(Me)CO2H	96	1090	NCf	11
10	−CO2H	213	241	482	1	2
11	−CH2CO2H	681	781	4040	1	6

^aPDE4D7-S129D is a dimeric isoform of PDE4D that contains a UCR1 mutation (S129D) that mimics PKA phosphorylation.

^bPDE4B1-S133D is a dimeric isoform of PDE4B that also contains a UCR1 mutation (S133D) that mimics PKA phosphorylation.

^cPDE4D7-S129(wt) is the native isoform of PDE4D7 that lacks the UCR1 phosphorylation mimetic mutation.

^dB/D is the ratio of IC₅₀ for PDE4B1-S133D/PDE4D7-S129D.

^eBasal/Activated is the ratio of IC₅₀ for PDE4D7-S129(wt)/PDE4D7-S129D.

^fNC -Not calculated as IC₅₀ >10,000 nM. See experimental section for methods and detailed synthetic procedures.