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. Author manuscript; available in PMC: 2024 Sep 14.
Published in final edited form as: J Med Chem. 2023 Aug 21;66(17):12249–12265. doi: 10.1021/acs.jmedchem.3c00806

Table 1.

Binding Affinities of Compounds 5a–v at Four Subtypes of the hARs

graphic file with name nihms-1969160-t0011.jpg
compd no.
 X
 Y
 R1
 R2
 Ki value (nM ± SEMa or % displacement at 10 μMb)
hA1AR hA2AAR hA2BAR hA3AR
 5a O O H 1-hexyne   183 ± 28  18.0 ± 5.5  327 ± 32  15.5 ± 2.9
 5b O O CH3 1-hexyne 3030 ± 50  50.5 ± 12.1    76 ± 1%    2.9 ± 0.7
 5c O O 3-I-Bn 1-hexyne  13 ± 1%   579 ± 53   4 ± 2%   199 ± 20
 5d = 4 O S H 1-hexyne   392 ± 99    7.7 ± 0.5  834 ± 11  15.6 ± 1.6
 5e O S CH3 1-hexyne 2310 ± 600   126 ± 18    52 ± 1%    2.9 ± 0.5
 5f O S 3-I-Bn 1-hexyne 2580 ± 460   513 ± 153   2 ± 3%    8.9 ± 4.8
 5g S O H 1-hexyne  46 ± 1%  13.2 ± 0.2   1973 ± 251   119 ± 39
 5h S O CH3 1-hexyne  17 ± 9%   159 ± 17    41 ± 2%  53.5 ± 16.9
 5i S O 3-I-Bn 1-hexyne  11 ± 7%    5 ± 5%   3 ± 2%    2 ± 8%
 5j S S H 1-hexyne    494 ± 122  61.4 ± 4.1   27 ± 2%   150 ± 6
 5k S S CH3 1-hexyne  11 ± 3% 2820 ± 1080    11 ± 2%   206 ± 26
 5l S S 3-I-Bn 1-hexyne    1 ± 0.2%    2 ± 2%   3 ± 3%  12 ± 5%
 5m S O H Cl 3890 ± 650   140 ± 10    53 ± 3%   855 ± 157
 5n S O CH3 Cl  49 ± 1%   752 ± 67    46 ± 1%  94.6 ± 45.2
 5o S O 3-I-Bn Cl 4900 ± 1070   336 ± 108    51 ± 1%  89.7 ± 20.4
 5p S S H Cl 1980 ± 140   459 ± 46    62 ± 3%   294 ± 80
 5q S S CH3 Cl  26 ± 4%   955 ± 704    17 ± 1%   138 ± 10
 5r S S 3-I-Bn Cl  50 ± 2%   720 ± 9    17 ± 2%   137 ± 28
 5s S O H tyramine  46 ± 3%   112 ± 6  227 ± 41 1650 ± 100
 5t S O CH3 tyramine 5330 ± 340   468 ± 28  713 ± 88   445 ± 148
 5u S S H tyramine 8050 ± 910   946 ± 94  608 ± 81 3010 ± 1140
 5v S S CH3 tyramine  47 ± 2%   917 ± 59  579 ± 135   106 ± 27
 3ac S H 1-hexyne  39 ± 10%  7.19 ± 0.6 N.D.d  11.8 ± 1.3
 3bc O H 1-hexyne   740 ± 430  63.2 ± 15 N.D.d   138 ± 44
a

All binding experiments were performed using adherent CHO cells and HEK293 cells stably transfected with cDNA encoding the appropriate hAR binding was carried out using 1 nM 25, 10 nM 26, 25 nM 27, and 0.2 nM 28 as radioligands for A1, A2A, A2B, and A3ARs, respectively. Values are expressed as mean ± SEM, n ± 3–4 (outliers eliminated), and are normalized against a nonspecific binder, 29.

b

When a percent value is shown, it refers to the percent inhibition of a specific radioligand binding at 10 μM, with nonspecific binding defined using 10 μM of 29.

c

Ref 18.

d

Not determined.