Relationship between the structure, bioactivity, metabolic stability, and cytochrome P450 (CYP) inhibition for the synthesized pyrrolidine-scaffold compounds.
| |||||
|---|---|---|---|---|---|
| Code | R | % HBV DNA remaining | CLint (μL per min per mg protein) | % CYP inhibition at 10 μM | |
| 0.1 μM | 1 μM | ||||
| CU01 |
|
— | 59 | 14.4 | NIa |
| CU02 |
|
— | 48 | 14.5 | CYP2B6 (50%), CYP2C19 (53%) |
| CU03 |
|
— | 44 | 9.2 | CYP2C9 (62%), CYP2C19 (63%), CYP2D6 (51%) |
| EC50 = 447 nM | |||||
| CU04 |
|
— | 67 | 1.1 | CYP2A6 (57%), CYP2C8 (55%), CYP2D6 (82%) |
| CU05 |
|
— | 47 | 2.9 | CYP2B6 (65%), CYP2C9 (87%) |
| CU06 |
|
— | 28 | 4.6 | CYP2B6 (81%), CYP2C9 (67%), CYP2D6 (89%), CYP3A4/5 (76%) |
| CU07 |
|
— | 77 | 6.2 | NI |
| CU08 |
|
43 | 0.5 | CYP2B6 (61%), CYP2C9 (53%) | |
| CU09 |
|
76 | 31 | 5.7 | NI |
| CU10 |
|
91 | 39 | 7.1 | CYP2C9 (90%) |
| CU11 |
|
45 | 32 | 6.3 | NI |
| EC50 = 35 nM | |||||
a
NI is no inhibition; values were less than 20%.