Table 1. Comparison of Physicochemical Properties for CNS Drugs, FDA-Approved Kinase Inhibitors, and EGFR Kinase Inhibitors.
| Physicochemical property | CNS drugs (preferred range, n = 317)a | CNS drugs (median, n = 119)b | FDA-approved protein kinase inhibitors (median, n = 49)c,d | Clinical EGFR kinase inhibitors (median, n = 25)c,d,e |
|---|---|---|---|---|
| MW | 250–355 | 305 | 486 | 491 |
| clogP | 2.1–4.4 | 2.8 | 4.2 | 4.5 |
| clogD7.4 | 1.2–3.1 | 1.7 | 3.3 | 3.9 |
| HBD | 0–1 | 1 | 2 | 2 |
| HBA | 2–3 | N/A | 7 | 7 |
| TPSA (Å2) | 25–60 | 45 | 94 | 89 |
| NRB | 1–4 | N/A | 6 | 8 |
| Most basic center (pKa) | 7.9–10.7 | 8.4 | 7.1 | 7.7 |
a
Preferred ranges for physicochemical properties from ref (13).
b
Median values from ref (14).
c
See Supporting Information for more details on how these values were compiled.
d
For at least 7 out of 49 FDA-approved kinase inhibitors, brain-penetration data has been reported.12
e
EGFR kinase inhibitors approved by any agency or in clinical development (noncomprehensive). N/A, no data provided.