Table 1.

Receptor-Binding Profiles of Truncated 1′-Homologated Adenosine Derivatives 4a–4t

cpd	X	Y	R	hA3AR Ki (nM) or % replacementa	PPARα % replacementb at 30 μM (%)	PPARγ Ki (μM) or % replacementb	PPARδ Ki (μM) or % replacementb
1				4.16	35.6	3.33 ± 1.67	0.0106 ± 0.015
4a	S	Cl	F	17% at 10 μM	15.5	3.89 ± 0.47	1.91 ± 0.39
4b	S	Cl	Cl	13% at 10 μM	12.8	34.1% at 30 μM	7.8% at 30 μM
4c	S	Cl	Br	21% at 10 μM	3.0	4.07 ± 0.86	0.592 ± 0.26
4d	S	Cl	I	10% at 10 μM	20.4	1.23 ± 0.25	0.106 ± 0.031
4e	S	H	F	9% at 10 μM	25.6	24.4% at 30 μM	0.8% at 30 μM
4f	S	H	Cl	9% at 10 μM	7.7	24.9% at 30 μM	10.0% at 30 μM
4g	S	H	Br	6% at 10 μM	5.4	33.5% at 30 μM	9.9% at 30 μM
4h	S	H	I	14% at 10 μM	9.4	39.2% at 30 μM	5.2% at 30 μM
4i	S	−C≡CCH3	F	2% at 10 μM	15.5	7.66 ± 0.65	13.8% at 30 μM
4j	S	−C≡CCH3	Cl	1% at 10 μM	12.6	41.7% at 30 μM	3.8% at 30 μM
4k	S	−C≡CCH3	Br	12% at 10 μM	12.8	7.04 ± 0.40	15.3% at 30 μM
4l	S	−C≡CCH3	I	2% at 10 μM	24.0	7.30 ± 1.01	15.9% at 30 μM
4m	O	Cl	F	2% at 10 μM	5.0	9.0% at 30 μM	7.3% at 30 μM
4n	O	Cl	Cl	1% at 10 μM	3.6	7.66 ± 2.45	0.504 ± 0.29
4o	O	Cl	Br	14% at 10 μM	23.2	9.55 ± 6.61	1.43 ± 0.67
4p	O	Cl	I	3% at 10 μM	0.3	3.56 ± 0.75	0.374 ± 0.036
4q	O	H	F	1% at 10 μM	1.4	13.3% at 30 μM	14.6% at 30 μM
4r	O	H	Cl	1% at 10 μM	8.3	0.8% at 30 μM	10.6% at 30 μM
4s	O	H	Br	14% at 10 μM	5.6	4.1% at 30 μM	16.5% at 30 μM
4t	O	H	I	3% at 10 μM	1.7	16.0% at 30 μM	6.5% at 30 μM
26				ND	3.5	0.096 ± 0.049	14.7% at 30 μM
27				ND	44.9	38.5% at 30 μM	0.00608 ± 0.0055
28				ND	12.4	59.9% at 30 μM	0.00465 ± 0.0023

^aBinding affinities of 4a–4h to human A₃ AR were previously reported.^6,23

^bBinding affinities to PPARs were determined based on TR-FRET-based PPAR competitive binding assays. K_i, inhibition constant; ND, not determined.