Table 1.

The PDE10A inhibition activity (IC₅₀ nM) of cinnoline analogues

Compound#	R3	R2	R3	R4	IC50 (nM)a
13a	-OCH3	-OCH3	-H	CH3	18.4 ± 6.0
13b	-OBn	-OCH3	-H	CH3	4,250 ± 520
13c	-OCH3	-OCH3	-H	pyridin-3-yl	14.0 ± 2.0
13d	-OBn	-OCH3	-H	pyridin-3-yl	1,550 ± 260
14a	-OH	-OCH3	-H	CH3	10,800 ± 1,500
14b	-OH	-OCH3	-H	pyridine-3-yl	6,620 ± 600
26a	-OCH3	-OCH3	-CH3	pyridine-3-yl	1.52 ± 0.18
26b	-OCH3	-OCH3	-CH3	2-fluoro-pyridin-5-yl	2.86 ± 0.10
26c	-O-CH2-O-		-CH3	2-fluoro-pyridin-5-yl	NAb
26d	-H	-H	-CH3	2-fluoro-pyridin-5-yl	NAb
26e	-OCH3	-OCH3	-CH3	2-chloro-pyridin-5-yl	9.8 ± 1.3
26f	-OBn	-OCH3	-CH3	2-fluoro-pyridin-5-yl	350 ± 23
26g	-OCH3	-OCH3	-Cl	pyridin-3-yl	5.52 ± 0.33
26h	2-(oxymethyl)-quinolinyl	-OCH3	-CH3	2-fluoro-pyridin-5-yl	518 ± 86
26i	fluoropropoxy	-OCH3	-CH3	2-fluoro-pyridin-5-yl	79.3 ± 3.6

^aIC₅₀ value (mean ± SD nM) were determined in at least three experiments;

^bNA = no inhibition activity