Table 2. In Vitro DMPK Data of Pyrazolopyrimidine Analoguesa.
| LogD7.4 | Aq. Sol. (μM) | H. Mics. CL.(μL/min/mg) | R. Hep. CL (μL/min/106 cells) | H. PPB (%) | |
|---|---|---|---|---|---|
| 1 | 4.2 | 0.07 | 63.22 | 105.60 | 99.9 |
| 2 | 4.0 | 0.40 | ND | 59.03 | 99.80 |
| 3 | 4.3 | 0.90 | 49.19 | 67.66 | 99.8 |
| 10a | 4.3 | 0.30 | 24.49 | 75.43 | ND |
| 10b | 3.3 | 0.50 | 48.86 | 41.25 | 99.0 |
| 10c | 3.7 | 0.01 | 8.76 | 46.48 | 99.7 |
| 10d | 2.0 | 561 | 261.80 | 109.60 | 77.0 |
| 15a | 4.0 | 0.60 | 83.97 | 113.20 | 99.9 |
| 15b | 4.1 | 1.00 | 59.33 | 86.16 | 99.9 |
| 15c | 4.5 | 5.00 | 8.76 | 156.60 | 97.9 |
| 15d | 2.3 | 11.0 | 74.15 | >300.00 | 88.0 |
| 15e | 3.0 | 2.00 | 12.08 | 147.80 | 96.6 |
| 15f | 3.3 | 2.00 | 21.78 | 27.58 | 99.8 |
| 15g | 2.7 | 43.0 | 44.83 | 10.31 | 91.8 |
| 15h | 2.3 | 30.0 | 243.60 | 144.90 | 97.4 |
| 15i | 4.3 | 2.0 | 44.62 | 26.37 | 99.5 |
| 15j | 2.4 | 21.0 | 23.65 | 71.84 | ND |
| 15k | 4.0 | 6.0 | 37.48 | 45.53 | 99.6 |
a
Notes: Aq. Sol. = aqueous solubility in pH7.4 PBS; H. Mics. CL = intrinsic human microsomal clearance measured in vitro; R. Hep. CL = intrinsic Rat hepatocyte clearance measured in vitro; ND = not determined.