Table 5. ADME and PK Data for Lead Compoundsa.
| cmp | 4 | 5 | 6 | 7 | 9 | 14 |
| solubility pH 6.8 μM | 120 | 22 | 7 | 12 | 150 | 370 |
| LM CLint (m/r) [μL/min/mg] | 145/37 | 65/<25 | 55/<25 | 79/66 | 84/28 | 91/48 |
| LM scaled CLint [mL/min/kg] (m/r) | 571/67 | 256/45 | 217/45 | 311/119 | 331/50 | 358/86 |
| fu plasma [%] (m/r) | 1.4/3.9 | 0.6/1.3 | 0.9/1.4 | 1.0/1.6 | 7.3/10.6 | 7.6/20.1 |
| CLp [mL/min/kg] (m/r) | 37/22 | 12/5 | 19/7 | 17/9 | 14/19 | 66/29 |
| CLu [mL/min/kg] (m/r) | 2643/564 | 2000/385 | 2111/500 | 1700/563 | 192/179 | 868/144 |
| AUCPO [μM·h] (m/r) | 3.6/6.3 | 4.9*/16* | 6.8/23 | 5.2*/17* | 5.4*/14 | 0.8/2.5 |
| AUCIV [μM·h] (m/r) | 1.2/2.0 | 3.2/7.8 | 2.3/6.3 | 2.3/4.4 | 3.3/2.5 | 0.7/1.6 |
| %F m/r | 58/63 | 50*/69* | 60/76 | 76*/128* | 53*/109 | 22/30 |
a
Solubility: Miniaturized shake flask solubility as described in the Experimental Section; Clint assay described in the Experimental Section; fu,plasma from PPB; LM scaled Clint = (LM Clint·SF1·SF2)/1000 with SF1 (mg protein per g liver) m,r = 45, SF2 (g liver per kg BW); m = 87.5, SF2 r = 40. Unbound clearance: Clu = Clp/fu, with Clp observed clearance. Mouse and rat PK 1 mpk IV/5 mpk PO. *(5, 7, 9 PK for 1 mpk IV and 3 mpk PO).