Table 6.
SAR of meta-aryl aniline ring substitutions
| ||||
|---|---|---|---|---|
| Compound | R4 | Tb IC50,b μM | Hs IC50,c μM | Tb427 EC50,d μM |
| 35 | Ph | 3.3 (2.8–3.9) | 30% at 63 | 4.5 (2.1–9.4) |
| 91 | 4-FPh | 1.1 (0.95–1.2) | >21 | 1.6 (0.94–2.8) |
| 92 | 4-ClPh | 1.7 (1.6–2.0) | >63 | 2.2 (1.8–2.7) |
| 93 | 4-MeOPh | 2.3 (2.1–2.6) | >180 | 4.5 (3.1–6.6) |
| 94 | 4-MePh | 4.6 (4.0–5.3) | >63 | 4.3 (3.3–5.7) |
| 95 | 4-CF3Ph | 4.7 (3.9–5.7) | >21 | 2.0 (1.4–3) |
| 96 | 4-CNPh | 7.6 (3.2–18) | >7 | 1.0 (0.96–1.1) |
| 97 | 4-AcPh | 28% at 21 | >21 | 6.7 (4.1–11) |
| 98 | 4-HOPh | 143 (115–178) | >180 | 9.7 (7.5–13) |
| 99 | 4-PhPh | 167 (150–190) | >180 | 0.91 (0.82–1) |
| 100 | 4-NMe2Ph | 34% at 180 | >180 | 5.0 (4.2–6) |
| 101 | 2-ClPh | 26 (22–33) | >180 | 8.5 (7.6–9.5) |
| 102 | 3-ClPh | 81 (57–114) | >180 | 1.9 (1.6–2.3) |
| 103 | 3,4-(Cl)2Ph | 102 (82–125) | >180 | 2.9 (1.3–3.6) |
| 104 | 3-Cl-4-FPh | 157 (95–260) | >180 | 3.2 (2.8–3.7) |
| 105 | 3-CF3-4-ClPh | 53 (46–61) | >180 | 1.5 (1–2.2) |
| 106 | 3,5-(CF3)2Ph | 28 (25–31) | >180 | 0.53 (0.47–0.59) |
| 107 | 2-naphthyl | 57 (51–64) | >180 | 1.7 (1.4–2) |
| 108 | 9-phenanthrenyl | >180 | >180 | 1.8 (1.5–2.1) |
| 109 | 5-benzo-1,3-dioxolyl | 6.2 (4.6–8.3) | >21 | 2.3 (1.6–3.2) |
| 110 | 5-benzofurazanyl | 27 (21–35) | >180 | 0.57 (0.13–2.5) |
| 111 | 3-furanyl | 7.4 (6.2–8.7) | 30% at 180 | 7.1 (5.7–8.8) |
| 112 | 2-benzofuranyl | 23% at 63 | >63 | 1.4 (1.4–1.5) |
| 113 | 3-thiopheneyl | 26 (22–32) | 30% at 180 | 29 (23–35) |
| 114 | 2-benzothiopheneyl | 41 (36–46) | >180 | 1.6 (1.5–1.8) |
| 115 | 5-thiazolyl | 42% at 21 | >21 | 3.6 (3.1–4.1) |
| 116 | N-Me-4-pyrazolyl | 164 (132–203) | >180 | 6.7 (4.7–9.6) |
| 117 | 5-pyrimidinyl | >180 | >180 | 58 (33–100) |
| 118 | 2.7 (2.2–3.4) | >180 | 1.3 (1.1–1.5) | |
All compounds have pKa(N1)a of 7.3.
a, b, c, d
See footnotes for Table 1.