Table 5.

AR Affinities and Selectivities of Tricyclic Purinone Derivatives

compd	R1	R2	R4	R7	R8	Ki (μM) ± SEM or % displacement at indicated concentration (in brackets)
						A1 affinity rat brain cortical membranes1 [3H]CHA	A2A affinity rat brain striatal membranes1 [3H]CGS21680	A3 affinity human recombinant receptors [125I]AB-MECA
2-Unsubstituted Imidazopurinones
15	methyl	H	H	H	H	65.5 ± 7.6	40.9 ± 6.3	>10a
16	methyl	H	benzyl	H	H	24% (30 μM)	16.1 ± 3.8	ndb
17	methyl	H	methyl	H	H	79.6 ± 0.6	20.7 ± 3.0	40% (10 μM)
R-18	methyl	H	methyl	H	(R)-methyl	14% (3 μM)	12% (30 μM)	nd
S-18	methyl	H	methyl	H	(S)-methyl	10% (10 μM)	46% (30 μM)	nd
RS-19	methyl	H	methyl	H	(R,S)-ethyl	46% (250 μM)	16.2 ± 0.6	28% (100 μM)
R-19	methyl	H	methyl	H	(R)-ethyl	75.5 ± 4.5	28.3 ± 5.4	nd
S-19	methyl	H	methyl	H	(S)-ethyl	50% (250 μM)	10.9 ± 1.2	nd
RS-20	methyl	H	methyl	(R/S)-methyl	H	59 ± 8	64.6 ± 9.8	>10a
R-20	methyl	H	methyl	(R)-methyl	H	23 ± 4	50.4 ± 13.4	nd
S-20	methyl	H	methyl	(S)-methyl	H	70 ± 6	12.0 ± 1.9	nd
2-Substituted Imidazopurinones
21	methyl	phenyl	H	H	H	1.83 ± 0.9	11.9 ± 1.6	0.047 ± 0.0048
22	methyl	phenyl	methyl	H	H	9.7 ± 2.6	20.3 ± 2.6	3.33 ± 0.72
RS-23	methyl	phenyl	methyl	H	(R,S)-ethyl	6.1 + 0.8	19.2 ± 3.9	17% (10 μM)
R-23	methyl	phenyl	methyl	H	(R)-ethyl	17.5 ± 5.0	36.3 ± 1.2	nd
S-23	methyl	phenyl	methyl	H	(S)-ethyl	4.7 ± 0.3	16.2 ± 4.6	nd
RS-24	H	phenyl	methyl	H	(R,S)-ethyl	0.265 ± 0.1	3.1 ± 0.5	nd
R-24 (PSB-11)	H	phenyl	methyl	H	(R)-ethyl	0.44 ± 0.1	2.1 ± 0.14	0.0023 ± 0.0011
S-24	H	phenyl	methyl	H	(S)-ethyl	0.115 + 0.001	3.33 ± 0.93	0.0098 ± 0.0038
R-25	methyl	styryl	methyl	H	(R)-ethyl	21.7 ± 3.8	0.547 ± 0.035	1.70 ± 0.48
S-25	methyl	styryl	methyl	H	(S)-ethyl	14.9 ± 2.6	0.424 ± 0.007	30.6 ± 8.3
R-26	H	styryl	methyl	H	(R)-ethyl	0.95 ± 0.15	0.89 ± 0.01	0.64 ± 0.199
S-26	H	styryl	methyl	H	(S)-ethyl	0.73 ± 0.13	0.67 ± 1.73	>10a
Ring-Enlarged Analogues of Imidazopurinones
27	methyl	H	methyl			43.2 ± 13.4	28.5 ± 5.2	>10a
28	methyl	Cl	methyl			10.5 ± 6.1	11.9 ± 0.87	nd
29	methyl	H	methyl			19.8 ± 9.5	18.5 ± 1.3	>10a
30	methyl	H	methyl			60.3 ± 8.1	51 ± 4	>10a
Xanthine Derivatives (for Comparison)
	R7	R8	R3	R1	name
31	methyl	H	methyl	methyl	caffeine	4139	4339	13.37
32	methyl	phenyl	methyl	methyl	8-phenylcaffeine	1540	2540	nac
33	H	phenyl	methyl	methyl	8-phenyltheophylline	0.08939	0.8339	na
34	methyl	styryl	methyl	methyl	8-styrylcaffeine	3.941	0.09441	na
35	H	styryl	methyl	methyl	8-styryltheophylline	0.6541	0.2941	na

^and = not determined.

^bLess than 10% displacement at 10 μM.

^cData not available.