Table 1. mGlu5 Potency and Rat Brain Penetration SAR in 1,2,4-Triazole Series.
entry | series | R1 | X | Y | R2 | R3 | mGlu5 IC50 (nM) | rat B/P ratio |
---|---|---|---|---|---|---|---|---|
1 | I | Cl | CHMe (R) | O | Me | A (Z = CH) | 8 | 0.03 |
2 | III | Cl | CHMe (R) | O | Me | A (Z = CH) | 6 | 0.01 |
3 | III | Cl | CHMe (R) | O | Me | A (Z = N) | 5 | 0.075 |
4 | II | Cl | C=O | NMe | Me | B | 37 | 0.26 |
5 | II | Cl | C=O | NMe | Me | C (Z = N; R4 = H) | 62 | 0.19 |
6 | II | Cl | CH2 | NMe | Et | C (Z = N; R4 = H) | 13 | <0.01 |
7 | II | Me | CH2 | NEt | Me | C (Z = N; R4 = H) | 45 | 0.01 |
8 | II | Cl | CH2 | NEt | Me | C (Z = CH; R4 = Me) | 65 | <0.01 |
9 | II | Me | CH2 | NEt | Me | C (Z = CH; R4 = Me) | 112 | 0.22 |
10 | II | Cl | CH2 | NMe | Me | D | 20 | 0.16 |
11 | I | Me | CH2 | NEt | Me | C (Z = CH; R4 = Me) | 75 | <0.01 |