Table 1.

Affinities of 1,4-Dihydropyridine Derivatives in Radioligand Binding Assays at A₁, A_2A, and A₃ Receptors^a–c

				Ki (μM) or % inhibition
compd	R3	R4	R5	rA1a	rA2Ab	hA3c	rA1/hA3
1b e	OCH2CH3	Ph-C≡C-	OCH2Ph	40.1 ± 7.5	d (10−4)	0.0314 ± 0.0028	1300
2 e	OCH2CH3	Ph-CH=CH- (trans)	OCH2CH3	5.93 ± 0.27	4.77 ± 0.29	0.108 ± 0.012	55
3 e	OCH2CH3	Ph-C≡C-	OCH2CH3	11.0 ± 0.1	26 ± 12% (10−4)	0.0766 ± 0.0151	140
4 e	OCH2Ph	Ph-C≡C-	OCH2CH3	24 ± 4% (10−4)	d (10−4)	0.169 ± 0.026	>600
5	OCH2Ph	Ph-C≡C-	OCH2Ph	d (10−4)	d (10−4)	0.195 ± 0.038	>500
6, 2-Ph	OCH2CH3	Ph-C≡C-	OCH2Ph	36 ± 11% (10−4)	d (10−4)	20% (10−5)
7, 2-Ph	OCH2Ph	Ph-C≡C-	OCH2Ph	19 ± 8% (10−4)	d (10−4)	d (10−5)
8a	O(CH2)2OCH3	Ph-C≡C-	OCH2Ph	48.7 ± 7.3	14 ± 7% (10−4)	0.001 91 ± 0.000 31	25 000
8b	O(CH2)2OCH3	Ph-C≡C-	OCH2Ph-4–NO2	23.6 ± 9.1	d (10−4)	0.003 08 ± 0.001 22	7700
9	O(CH2)2OH	Ph-C≡C-	OCH2Ph	10.6 ± 1.9	d (10−4)	0.002 07 ± 0.0012	5100
10	O(CH2)2SH	Ph-C≡C-	OCH2Ph	d (10−4)	d (10−4)	0.197 ± 0.076	>500
11	S(CH2)2SH	Ph-C≡C-	OCH2Ph	38 ± 11% (10−4)	d (10−4)	0.178 ± 0.018	>500
12	O(CH2)2S(CH2)2Si(CH3)3	Ph-C≡C-	OCH2Ph	13 ± 7% (10−4)	30% (10−4)	1.98 ± 0.64	>50
13	OCH2(4-SO2F)Ph	Ph-C≡C-	OCH2CH3	d (10−4)	18	0.341 ± 0.091	>300
14	OCH2(4-SO2NH2)Ph	Ph-C≡C-	OCH2CH3	16.9 ± 5.0	13.5 ± 1.3	0.187 ± 0.033	90
15	OCH2(4-CO2CH2CCl3)Ph	Ph-C≡C-	OCH2CH3	19% (10−4)	5.99 ± 1.67	8.93 ± 5.63	>1
16	OCH2Ph-4-CO–NH(CH2)2NH2	Ph-C≡C-	OCH2CH3	6.65 ± 1.35	7.85	0.128 ± 0.018	52
17	OCH2(4-CO2H)Ph	Ph-C≡C-	OCH2CH3	16.0 ± 2.1	<1 (shallow curves)	0.799 ± 0.297	20
18	OCH2Ph-4-CO-NH(CH2)2NH-biotin	Ph-C≡C-	OCH2CH3	38 ± 2% (10−4)	16 ± 8% (10−4)	0.599 ± 0.151	>100
19 f	OCH2CH3	Ph-C≡C-	OCH2(4-SO2F)Ph	41 ± 3% (10−4)	20% (10−4)	0.002 42 ± 0.000 32	>30 000
20	OCH2CH3	Ph-C≡C-	OCH2(4-SO2NH2)Ph	14.4 ± 2.4	22.0 ± 6.1	0.292 ± 0.030	49
21	OCH2CH3	Ph-C≡C-	OCH2 (4-CO2CH2CCl3)Ph	33 ± 6% (10−4)	11% (10−4)	5.00	>20
22 g	OCH2CH3	Ph-C≡C-	OCH2Ph-4-CO-NH(CH2)2NH2	3.0	39 ± 4% (10−4)	0.697 ± 0.259	4.3
23	OCH2CH3	Ph-C≡C-	OCH2 (4-CO2H)Ph	19.0 ± 5.3	8.22 ± 3.76	d (10−6)

^aDisplacement of specific [³H]R–PIA binding in rat brain membranes, expressed as K_i ± SEM (n = 2–5), or as a percentage of specific binding displaced at the indicated concentration (M).

^bDisplacement of specific [³H]CGS 21 680 binding in rat striatal membranes, expressed as K_i ± SEM (n = 2–6), or as a percentage of specific binding displaced at the indicated concentration (M).

^cDisplacement of specific [¹²⁵I]AB-MECA binding at human A₃ receptors expressed in HEK cells, in membranes, expressed as K_i ± SEM (n = 2–4).

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

^eValues taken from Jiang et al. (12) and references therein.

^fBound to human A₃ receptors irreversibly (see Figure 2), K_i value is apparent.

^gSame as compound 25 in Jiang et al. (12) K_i values have been redetermined.