Table 2.
mGlu5 potency and rat brain penetration SAR in constrained cyclic amine 1,2,4-triazole analogues
Entry | Series | R1 | R2 | mGlu5 IC50 (nM) | Rat B/P Ratio |
---|---|---|---|---|---|
20 | I | 3-chlorophenyl | A (Z = CH; R3 = CO2NH2) | 11 | < 0.01 |
21 | I | 3-chlorophenyl | A (Z = N; R3 = NH2) | < 3 | 0.085 |
22 | I | 3-chlorophenyl | A (Z = N; R3 = NMe2) | 39 | 0.285 |
23 | I | 5-chlorothiophen-3-yl | B (Z = N; R3 = H) | 39 | <0.01 |
24 | II | 5-chlorothiophen-3-yl | B (Z = N; R3 = H) | 34 | 0.06 |
25 | I | 5-chlorothiophen-3-yl | B (Z = N; R3 = Me) | 61 | 0.16 |
26 | II | 3-chlorophenyl | B (Z = N; R3 = H) | 32 | < 0.01 |
27 | II | 3-chlorophenyl | B (Z = CH; R3 = Me) | 39 | <0.01 |
28 | III | 3-chlorophenyl | B (Z = N; R3 = H) | 46 | not reported |