Table 2.

Experimental data for optimized dual‐target ligands.

Cmpd	Structure			Binding affinity[a]		Functional activity[a]
	R1	R2	R3	A2AAR	D2R	A2AAR	D2R
				Ki [μm]	Ki [μm]	Kb [μm]	EC50 [μm]	Emax [%]
2	CH3	CH3	H	1.2±0.1	0.90±0.08	–[b]	9.7±3.8	93±12
18	CH3	OCH3	H	0.37±0.05	0.39±0.03	–	26±14	89±18
19	CH3	Cl	H	0.42±0.04	0.51±0.05	–	23±9	82±22
20	CH3	Br	H	0.19±0.03	0.34±0.03	0.32±0.03	1.5±0.02	62±9
21	CH2CH3	OCH3	H	0.63±0.08	0.33±0.02	–	–	–
22	CH2CH3	Br	H	0.34±0.05	0.34±0.04	–	2.5±0.9	119±6
23	CH2CH2CH3	F	H	2.9±0.6	0.20±0.02	–	–	–
24	CH2CH2CH3	CH2CH3	H	11±3	0.82±0.18	–	–	–
25	CH2CH2CH3	CH3	H	0.99±0.24	0.34±004	–	0.75±0.07	81±5
26	CH2CH2CH3	OCH3	H	0.61±0.09	0.23±0.02	3.6±2.0	0.99±0.38	94±3
27	CH2CH2CH3	Br	H	0.39±0.05	0.53±0.18	0.51±0.24	0.18±0.03	89±4
28	CH2CH2CH3	OCH3	Cl	0.47±0.11	0.90±0.10	–	1.2±0.2	104±6
29	CH2CH2CH3	OCH3	CH3	0.46±0.04	0.67±0.07	1.9±0.7	0.98±0.01	105±5
30	CH2CH2CH3	OCH3	OCH3	0.16±0.03	0.37±0.03	0.72±0.25	0.18±0.04	77±5
31	CH3	CH3	H	1.6±0.3	0.63±0.05	–	5.2±2.6	88±13
32	CH3	Br	H	0.67±0.11	0.88±0.11	–	1.2±0.3	51±4
33	CH3	Br	H	1.1±0.2	2.2±0.3	–	5.0±2.8	81±6
37	CH3	OCH3	OCH3	0.30±0.05	1.3±0.2	–	31±12	103±3
39	CH2CH3	OCH3	CH3	1.3±0.2	2.0±0.3	–	28±9	107±6
40	CH2CH3	OCH3	OCH3	0.72±0.07	1.9±0.3	–	8.9±2.7	105±5

[a] Data represent mean values±SEM of three individual experiments each performed in duplicate. E_max values are relative (%) to the maximal effect of dopamine. [b] Not determined.