TABLE 2.

Summary data for A2A agonist pharmacology, physicochemical properties, and antagonist reversal rate

pEC₅₀ is derived from concentration-response curves using the GloSensor cAMP assay (Sample curves in Supplemental Fig. 2) measured at 20°C for 100 minutes. LogD_7.4 and log K_IAM are experimentally measured physicochemical properties used as indicators of, respectively, lipophilicity and membrane partitioning. Antagonist reversal t_1/2 to estimated agonist off-rate was derived from normalized antagonist reversal curves (one-phase exponential decay) shown in Fig. 3. Curves were constrained to give a minimal response of “0” as incomplete reversal observed over the time-course. Accurate reversal t_1/2 values were difficult to derive for THESE data, but we can say with confidence that t_1/2 > 100 minutes. pEC₅₀ values and reversal half-life estimates are an average of 3 or 4 experiments performed in triplicate.

Compound	pEC50	logD7.4	log KIAM	Antagonist Reversal t1/2 (min)
1aa	7.30 ± 0.19	0.6	1.13	5.50 ± 0.28
2bb	6.16 ± 0.13	N.T.	N.T.	8.14 ± 1.07
2cb	5.97 ± 0.19	2.6	2.31	4.48 ± 0.50
3ab	7.52 ± 0.06	−0.3	−0.57	5.80 ± 0.25
3ac	7.18 ± 0.14	< -0.8	−0.09	8.99 ± 0.19
3ad	5.70 ± 0.21	0.3	0.86	5.02 ± 0.37
3cd	8.32 ± 0.07	3.6	2.38	39.99 ± 4.41
3ce	6.74 ± 0.17	1.9	3.35	6.50 ± 0.85
3cf	5.91 ± 0.04	0.1	2.74	9.44 ± 3.28
3ag	7.53 ± 0.06	< -0.1	0.51	10.56 ± 0.91
3cg	9.04 ± 0.09	3.5	2.56	*309 ± 124
3dg	9.01 ± 0.13	1.8	1.86	38.29 ± 4.80
3eg	9.84 ± 0.05	2.25	2.08	63.34 ± 3.12
3ah	7.79 ± 0.08	< -1	0.66	11.31 ± 1.60
3ch	9.89 ± 0.10	0	2.87	*417 ± 86
3dh	9.35 ± 0.10	< -1.1	2.21	39.15 ± 9.84
3eh	9.48 ± 0.22	−0.7	2.42	*151 ± 32
4	7.93 ± 0.17	0	2.21	6.25 ± 0.72

N.T., not tested.