Table 1. Comparison of the CNS MPO Scores and Physicochemical Properties of Selected BTK Inhibitors.
| compound name | CNS MPO scorea | MW [g/mol] | tPSA [Å] | HBD | clog Pb,c | clog D (pH 7.4)b,c |
|---|---|---|---|---|---|---|
| Ibrutinib (1) | 3.52 | 440.2 | 99 | 2 | 4.1 | 3.6 |
| Tolebrutinib (2) | 3.44 | 455.2 | 95 | 2 | 4.7 | 3.7 |
| Fenebrutinib (3) | 3.35 | 664.4 | 121 | 2 | 2.4 | 2.3 |
| Evobrutinib (4) | 3.11 | 429.2 | 93 | 3 | 4.8 | 3.9 |
| Remibrutinib (5) | 2.19 | 507.2 | 110 | 3 | 3.2 | 3.8 |
| BIIB091 (6) | 3.30 | 542.3 | 128 | 2 | 1.9 | 2.4 |
| Optimal for CNS MPO score | 6 (max.) | <350 | 40 < x < 90 | 0 | <3.0 | <2.0 |
a
Basic pKa contribution is 1 across all entries.
b,c
MoKa was used to calculate clog P, clog D, and pKa.