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. Author manuscript; available in PMC: 2024 Jan 15.
Published in final edited form as: J Med Chem. 1996 Nov 8;39(23):4667–4675. doi: 10.1021/jm960457c

Table 1.

Affinities of Dihydropyridine and Pyridine Derivatives in Radioligand Binding Assays at A1, A2a, and A3 Receptorsa-f

graphic file with name nihms-1956238-t0007.jpg
Ki (μM) or % inhibitiond
compd R3 R4 R5 R6 rA1a rA2Ab hA3c rA1/hA3
5 e CH3 CH3 CH2CH3 CH3 32.6 ± 6.3 46.1 ± 6.8 32.3 ± 5.1 1.0
6 e CH3 CH3 CH2Ph CH3 6.45 ± 1.47 9.72 ± 0.63 2.78 ± 0.89 2.3
7 e CH3 CH2CH3 CH2CH3 CH3 7.52 ± 2.79 7.89 ± 2.87 13.6 ± 2.0 0.53
8 e CH3 PhCH=CH-(trans) CH2CH3 CH3 16.1 ± 0.5 49.3 ± 12.5 0.670 ± 0.195 24
9 CH2CH3 PhCH=CH-(trans) CH2CH3 CH3 4.65 ± 1.21 9.23 ± 3.60 0.887 ± 0.138 5.2
10 CH2CH3 PhCH=CH-(trans) CH2Ph CH3 13.7 ± 2.6 14 ± 4% (10−4) 3.13 ± 0.51 4.4
11 e CH2CH3 CH3 CH2CH3 Ph 25.9 ± 7.3 35.9 ± 15.3 7.24 ± 2.13 3.6
12 CH2CH3 CH2CH3 CH2CH3 Ph 21.5 ± 2.7 14.5 ± 3.5 8.49 ± 1.74 2.5
13 CH2CH3 CH3 CH2Ph Ph 26.0 ± 8.7 3.15 ± 0.96 1.75 ± 0.47 15
4 e CH2CH3 PhCH=CH-(trans) CH2CH3 Ph 5.93 ± 0.27 4.77 ± 0.29 0.108 ± 0.012 55
14 CH2CH3 PhCH=CH-(trans) CH2CH3 4-CH3Ph 14.9 ± 4.9 37 ± 2% (10−4) 9.13 ± 2.43 1.6
15 CH2CH3 PhCH=CH-(trans) CH2CH3 4-OCH3Ph 9.49 ± 1.99 d (10−4) 1.43 ± 0.37 6.6
16 CH2CH3 PhCH=CH-(trans) CH2CH3 4-ClPh 33.0 ± 7.5 12 ± 7% (10−4) 0.785 ± 0.272 42
17 CH2CH3 PhCH=CH-(trans) CH2CH3 4-NO2Ph 13.1 ± 1.6 40 ± 3% (10−4) 4.14 ± 0.51 3.2
18 CH2CH3 PhCH=CH-(trans) CH2CH3 3-furyl 5.49 ± 0.25 35 ± 6% (10−4) 0.907 ± 0.307 6.1
19 CH2CH3 PhCH=CH-(trans) CH2CH3 3-thienyl 7.52 ± 1.38 d (10−4) 0.407 ± 0.066 18
20 CH2CH3 2-OCH3PhCH=CH-(trans) CH2CH3 Ph 25.3 ± 2.4 17 ± 12% (10−4) 0.334 ± 0.059 76
21 CH2CH3 2-NO2PhCH=CH-(trans) CH2CH3 Ph 6.03 ± 1.39 d (10−4) 0.109±0.017 55
22 CH2CH3 4-NO2PhCH=CH-(trans) CH2CH3 Ph 23 ± 9% (10−4) 33% (10−4) 0.0585 ± 0.0164 >1700
23 CH2CH3 4-NH2PhCH=CH-(trans) CH2CH3 Ph 31 ± 3% (10−4) 26 ± 6% (10−4) 0.198 ± 0.047 >500
24 CH2CH3 (Ph)2C=CH- CH2CH3 Ph 1.20 ± 0.14 12 ± 6% (10−4) 1.42 ± 0.23 0.84
25 CH2CH3 PhC≡C- CH2CH3 Ph 11.0 ± 0.1 26 ± 12% (10−4) 0.0766 ± 0.0151 140
26 CH2CH3 PhCH=CH-(trans) CH2Ph Ph 35 ± 3% (10−4) 15 ± 3% (10−4) 0.0583 ± 0.0124 >1700
27 CH2CH3 4-NO2PhCH=CH-(trans) CH2Ph Ph 33 ± 1% (10−4) d (10−4) 0.0724 ± 0.0377 >1300
28 CH2CH3 PhC≡C- CH2Ph Ph 40.1 ± 7.5 d (10−4) 0.0314 ± 0.0028f 1300
29 CH2Ph PhCH=CH-(trans) CH2CH3 Ph d (10−4) 16 ± 11% (10−4) 0.142 ± 0.047 >700
30 CH2Ph 4-NO2PhCH=CH-(trans) CH2CH3 Ph d (10−4) d (10−4) 0.286 ± 0.038 >400
31 CH2Ph PhC≡C- CH2CH3 Ph 24 ± 4% (10−4) d (10−4) 0.169 ± 0.026 >600
32 e CH3 CH2CH3 7.41 ± 1.29 28.4 ± 9.1 4.47 ± 0.46 1.7
33 PhCH=CH-(trans) CH2CH3 2.49 ± 0.47 2.40 ± 0.22 2.80 ± 1.78 0.85
34 PhC≡C- CH2Ph 11.6 ± 4.8 43 ± 2% (10−4) 2.75 ± 0.78 4.2
a

Displacement of specific [3H]-(R)-PIA binding in rat brain membranes, expressed as Ki ± SEM in μM (n = 3–5), or as a percentage of specific binding displaced at the indicated concentration (M).

b

Displacement of specific [3H]CGS 21680 binding in rat striatal membranes, expressed as Ki ± SEM in μM (n = 3–6), or as a percentage of specific binding displaced at the indicated concentration (M).

c

Displacement of specific [125I]AB-MECA binding at human A3 receptors expressed in HEK cells, in membranes, expressed as Ki ± SEM in μM (n = 3–4).

d

Displacement of ≤ 10% of specific binding at the indicated concentration (M).

e

Values taken from van Rhee et al.16

f

Ki value at rat A3 receptors stably expressed in CHO cells1 found to be 3.53 ± 0.61 μM.