TABLE 3.

Structure-activity relationships for PDE12 inhibitors

Compound dose-response experiments were conducted and analyzed as described under “Experimental Procedures.”PDE12, PDE12 enzyme inhibition; CNOT6, CNOT6 enzyme inhibition; HeLa 2–5A, IFNα and poly(IC)-stimulated 2–5A levels in cell lysate; EMCV, EMCV CPE in HeLa Ohio cells; HRV16, inhibition of HRV16 infection of SAEC measured by imaging capsid protein. For inhibition assays, pXC₅₀ represents the negative log of the IC₅₀ in molar (pIC₅₀). For HeLa 2–5A, pXC₅₀ represents negative log of the inflection point of the increase (pEC₅₀). The values presented are the mean ± S.D. from the number of experiments shown in parentheses. For some of the replicate experimental determinations, a parameter fit was not obtained because the inflection point was outside the compound concentration range. These values had to be excluded from the reported mean: compound 1, PDE12 pIC₅₀ >9.1 n = 1; HeLa 2–5A pEC₅₀ >8.1 n = 2. Compound 2, HeLa 2–5A pEC50 <4.8 n = 2; compound 4, PDE12 pIC₅₀ <4.4 n = 1.