Table 1.
Inhibition of [3H]PIA binding to cerebral cortex membranes by adenosine analogs
| Adenosine analog | Inhibition [3H]PIA binding (Ki, nM)
|
||
|---|---|---|---|
| Rat | Calf | Guinea Pig | |
| 1 N6-1-Butyl- | 6.3 (4.4–9.1) | 10.7 (9.2–13.4) | 13.2 (9.5–18.3) |
| 2 N6-Cyclobutyl- | 0.84(0.59–1.2) | 1.7 (1.3–2.3) | 1.8 (1.2–2.6) |
| 3 N6-3-Pentyl- | 1.0 (0.69–1.5) | 1.6 (1.2–2.1) | 2.1 (1.4–3.2) |
| 4 N6-2-Methyl-2-propyl- | 20.4 (12.2–34) | 57 (33–100) | 42 (30–57) |
| 5 N6-Cyclopentyl- | 0.34 (0.27–0.41) | 0.69 (0.53–0.89) | 1.1 (0.87–1.4) |
| 6 N6-1-Methylcyclopentyl- | 1.4 (1.0–1.9) | 6.7 (4.7–9.4) | 5.1 (2.8–9.0) |
| 7 N6-Cyclohexyl- | 1.0 (0.69–1.6) | 1.4 (0.90–2.2) | 2.4 (1.6–3.7) |
| 8 N6-Cyclooctyl- | 5.4 (4.2–6.8) | 5.4 (4.5–6.5) | 8.1 (7.6–8.5) |
| 9 N6-Phenyl- | 16.4 (9.7–28) | 3.0 (1.6–5.7) | 110 (67–180) |
| 10 N6-Benzyl- | 175 (120–260) | 59 (48–73) | 350 (250–490) |
| 11 N6-2-Phenethyl- | 16.1 (12.3–21.0) | 3.5 (1.9–6.6) | 28.7 (20.1–41.0) |
| 12 N6-2-(3-Pyridylethyl)- | 10.4 (7.3–14.9) | 4.8 (3.6–6.4) | 76 (47–123) |
| 13 N6-2-(4-Pyridylethyl)- | 16.2 (8.9–29.4) | 2.7 (1.0–7.0) | 82 (64–106) |
| 14 N6-2-(2-Thienylethyl)- | 6.8 (2.5–17.5) | 1.9 (0.8–5.0) | 13.3 (9.2–19.4) |
| 15 N6-CH3NHCOCH2C6H4- | 13.2 (7.9–21.8) | 3.2 (2.2–4.6) | 32.9 (28.5–38.1) |
| 16 N6-CH3C6H4NHCOCH2C6H4- | 1.7 (0.77–3.9) | 1.0 (0.93–1.1) | 7.7 (6.2–9.5) |
| 17 N6-H2N(CH2)2NHCOCH2C6H4-NHCOCH2C6H4- (ADAC) | 1.3 (1.0–1.7) | 0.39 (0.27–0.57) | 14.1 (13.6–14.7) |
| 18 N6-R-1-Phenyl-2-propyl- (R-PIA) | 1.2(0.89–1.5) | 0.56 (0.45–0.70) | 3.6 (3.1–4.1) |
| 19 N6-S-1-Phenyl-2-propyl- (S-PIA) | 50 (44–57) | 12.2 (9.1–16.3) | 83 (59–117) |
| 20 N6-2-Methyl-2-propyl- (MePIA) | 130 (110–160) | 150 (130–180) | 610 (410–890) |
| 21 5′-N-Ethylcarboxamido- (NECA) | 7.8 (5.4–11.2) | 52 (40–68) | 6.3 (5.5–7.3) |
| 22 5′-N-Methylcarboxamido | 64 (42–83) | 770 (650–920) | 70 (50–97) |
| 23 5′-Carboxamido- | 59 (46–75) | 770 (520–1130) | 60 (43–83) |
| 24 2-Chloro- | 7.5 (6.1–9.1) | 92 (68–124) | 11.7 (6.1–22.4) |
| 25 2-Phenylamino- | 400 (220–730) | 1400 (950–2100) | 540 (510–580) |
| 26 N6-Cyclohexyl-NECA | 0.57 (0.35–0.93) | 1.4 (1.1–1.9) | 1.1 (0.80–1.5) |
| 27 N6-R-1-Phenyl-2-propyl-NECA | 0.51 (0.42–0.64) | 1.1 (0.69–1.7) | 4.6 (3.2–6.5) |
| 28 N6-S-1-Phenyl-2-propyl-NECA | 9.8 (6.7–11.5 | 8.9 (6.9–11.6) | 41 (37–47) |
Binding of 1 nM [3H]PIA was measured at 37°C. Values are geometric means with 95% confidence limits from n = 4–6 with rat and n = 3 with calf and guinea pig cerebral cortex membranes, respectively