Table 2. In vitro ADME/PK profiling of Series 1 and 3 compounds.
Compounds were profiled for aqueous solubility, LogD, microsomal stability (human liver microsomes, HLM), hepatic clearance (Rhep), plasma protein binding (PPB), and inhibition of the hERG channel. Compounds from Series 1 showed better solubility, LogD, and clearance than compounds from Series 3.
| Series 1 | Series 3 | |||||
|---|---|---|---|---|---|---|
| BRD9101 | BRD3969 | BRD65768 | BRD3482 | BRD6801 | BRD5449 | |
| Solubility (μM) | <1 | 49 | 121 | 22 | <1 | 16 |
| LogD | >4.8 | 3.6 | 3.3 | 2.9 | >4.3 | >4.4 |
| HLM (μL/min/mg) | 57.1 | 77.9 | 41.2 | ND | 208 | 465 |
| Rhep (μL/min/106 cells) | 67.8 | 61.7 | 23.6 | ND | 43 | 194 |
| PPB (% free) | <1 | 1.6 | 2.1 | 3.8 | <1 | <1 |
| hERG (% inh at 11 μM) | ND | 14 | 18 | ND | ND | ND |