Table1.

Representative hits clustered by different chemotypes, with their A_2AAR binding characteristics and predicted ICM Scores. Clusters are named as in Figure 3. The last column shows compounds in GLIDA database of ~30,000 GPCR ligands⁴³ with highest chemical similarity to the identified hits.

ID	Cluster	Chemical Structure	Ki µM	95% confidence interval	Maxa Inhibition %	LEb	ICM Scorec	Closest Analog in GLIDA (Tanimoto Distance)
9	A		0.032	(0.023–0.043)	80	0.38	−36.3
8	B		0.63	(0.12–3.3)	54	0.3	−34.3
15	B		0.06	0.0082–0.45)	91	0.45	−32.4
49	C		0.25	(0.21–0.3)	100	0.5	−36.4
35	C		0.64	(0.43–0.94)	96	0.4	−39.1
29	C		0.32	(0.25–0.4)	88	0.49	−37.5
26	C		0.53	(0.29–0.98)	90	0.45	−37.8
6	D		0.3	(0.15–0.62)	70	0.35	−35
14	D		1	(0.73–1.4)	78	0.35	−34.8
10	D		2.7	(1.4–5.3)	92	0.3	−35.6
50	E		0.8	(0.44–1.5)	78	0.39	−37.8
17	E		0.56	(0.19–1.6)	80	0.35	−38.4
21	I		2.9	(1.7–5.1)	66	0.4	−38.5

^aMaximum Inhibition was achieved at 10 µM concentration for compound 9 and at 32 µM for compound 15. All other compounds showed maximum inhibition at 1 mM.

^bExperimental ligand efficiency, kcal/mol , calculated as ligand binding energy per heavy atom.

^cPredicted ICM binding score, kJ/mol