Table 1. SAR of Tetrazole Compounds 11–67.
| compd | R1 | R2 | X | Ki (nM) | cLog D (pH 7.4) |
|---|---|---|---|---|---|
| 11 | methyl | 3-alkynyl-phenyl | H | 400 | 1.2 |
| 12 | methyl | 3-alkynyl-phenyl | 4-F | 140 | 1.6 |
| 13 | butyl | 3-alkynyl-phenyl | H | 45 | 2.7 |
| 14 | butyl | 3-alkynyl-phenyl | 4-F | 10 | 3.1 |
| 15 | butyl | benzodioxane-6-yl | 4-F | 3.3 | 2.1 |
| 16 | butyl | 4-methoxyphenyl | H | 50 | 1.9 |
| 17 | butyl | 2-naphthyl | H | 39 | 3.2 |
| 18 | butyl | 6-isoquinyl | H | 330 | 1.7 |
| 19 | butyl | 2-thienyl | H | 620 | 1.8 |
| 20 | ethyl | phenyl | H | 1800 | 1.0 |
| 21 | ethyl | 3-OMe-phenyl | H | 360 | 1.1 |
| 22 | ethyl | 4-OMe-phenyl | H | 220 | 0.9 |
| 23 | butyl | 3-OMe-phenyl | H | 44 | 2.1 |
| 24 | butyl | 3-OMe-phenyl | 5-F | 3.0 | 1.4 |
| 25 | ethyl | 3-OMe-phenyl | 5-F | 8.2 | 0.4 |
| 26 | ethyl | 4-OMe-phenyl | 5-F | 7.6 | 0.1 |
| 27 | butyl | 4-OMe-phenyl | 5-F | 3.0 | 1.1 |
| 28 | butyl | 4-OMe-phenyl | 5-Cl | 3.6 | 2.6 |
| 29 | ethyl | 3-isopropoxyphenyl | 5-F | 6.4 | 1.2 |
| 30 | ethyl | 2-F-phenyl | H | 950 | 1.1 |
| 31 | ethyl | 3-F-phenyl | H | 1400 | 1.0 |
| 32 | ethyl | 4-F-phenyl | H | 1200 | 1.1 |
| 33 | ethyl | 3-methylphenyl | H | 580 | 1.5 |
| 34 | butyl | 2-naphthyl | 4-F | 18 | 3.6 |
| 35 | butyl | 2-benzofuranyl | 4-F | 7.1 | 3.3 |
| 36 | ethyl | 2-quinolyl | 5-F | 56 | 0.3 |
| 37 | ethyl | 1,4-benzodioxane-6-yl | H | 42 | 0.8 |
| 38 | propyl | 1,4-benzodioxane-6-yl | H | 12 | 1.3 |
| 39 | butyl | 1,4-benzodioxane-6-yl | H | 7.0 | 1.8 |
| 40 | ethyl | 1,4-benzodioxane-6-yl | 4-F | 11 | 1.1 |
| 41 | isobutyl | 1,4-benzodioxane-6-yl | 4-F | 5.6 | 2.0 |
| 42 | propyl | 1,4-benzodioxane-6-yl | 4-F | 4.9 | 1.6 |
| 43 | butyl | 1,4-benzodioxane-6-yl | 5-F | 2.0 | 1.0 |
| 44 | butyl | 1,4-benzodioxane-6-yl | 4,6-difluoro | 45 | 1.7 |
| 45 | ethyl | 1,3-benzodioxol-5-yl | H | 130 | 1.0 |
| 46 | ethyl | 3-CF3-phenyl | H | 220 | 1.8 |
| 47 | ethyl | 4-CF3-phenyl | H | 110 | 1.8 |
| 48 | ethyl | 4-CF3-phenyl | 5-F | 5.7 | 1.1 |
| 49 | butyl | 4-CF3-phenyl | 5-F | 2.4 | 2.1 |
| 50 | butyl | 3-OCF3-phenyl | 5-F | 4.5 | 2.4 |
| 51 | ethyl | 4-OCF3-phenyl | 5-F | 6.9 | 1.2 |
| 52 | butyl | 4-OCF3-phenyl | 5-F | 7.7 | 2.2 |
| 53 | butyl | 4-OCF3-phenyl | 5-Cl | 19 | 3.6 |
| 54 | ethyl | 4-CF3SO2-phenyl | 5-F | 5.2 | 1.2 |
| 55 | ethyl | 3-hydroxyphenyl | 5-F | 26 | –0.3 |
| 56 | ethyl | 4-hydroxy-phenyl | 5-F | 22 | –0.4 |
| 57 | ethyl | 4-MeSO2-phenyl | H | 69 | –0.2 |
| 58 | ethyl | 4-MeSO2-phenyl | 5-F | 3.1 | –0.9 |
| 59 | isopropyl | 4-MeSO2-phenyl | 5-F | 17 | –0.6 |
| 60 | isobutyl | 4-MeSO2-phenyl | 5-F | 3.2 | –0.1 |
| 61 | cyclopentyl | 4-MeSO2-phenyl | 5-F | 5.4 | 0.0 |
| 62 | phenyl | 4-MeSO2-phenyl | 5-F | 2.2 | –0.8 |
| 63 | benzyl | 4-MeSO2-phenyl | 5-F | 0.9 | –0.8 |
| 64 | 2-(4-tolyl)-ethyl | 4-MeSO2-phenyl | 5-F | 2.5 | 0.2 |
| 65 | dioxolan-4-yl | 4-MeSO2-phenyl | 5-F | 28 | –1.4 |
| 66 | 3-pyridyl | 4-MeSO2-phenyl | 5-F | 4.0 | –1.5 |
| 67 | 4-pyridyl | 4-MeSO2-phenyl | 5-F | 17 | –1.4 |