Table 1. Profile of Five Lead Candidates 2–6 That Exhibited Improved Binding T_1/2, Good Specificity in PDE10A Enriched Region in CNS, and Good Brain Uptake.

			LC–MS/MS TOb
compd	PDE10A IC50 (nM)	binding T1/2 (fold)a	[AUCStr/Tha]c	[%ID/g]d
1	1.9	1×	9.4	1.2
2	1.7	6×	12.6	0.8
3	0.1	21×	8.7	0.8
4	0.7	32×	5.6	0.3
5	0.1	16×/61×e	23	1.2
6	0.3	85×	5.7	1.0

^aFold over 1. Binding T_1/2 values were calculated based on measured K_d using the formula: {T_1/2 = Ln(2)/k_d}.

^bLC–MS/MS study was conducted in Sprague–Dawley (SD) rats at n = 10 per group. The compounds were dosed i.v. and formulated in 100% DMSO.

^cRatio of AUC of compound in striatum (Str) over AUC of compound in thalamus (Tha) at t = 10 min after dosing.

^dPercentage of injected dose (ID) of compound in the striatum per gram of tissue sampled.

^eSee Supporting Information section for additional experimental data on 5.