| 20088516 |
Nugiel DA, Krumrine JR, Hill DC, Damewood JR Jr, Bernstein PR, Sobotka-Briner CD, Liu J, Zacco A, Pierson ME: De novo design of a picomolar nonbasic 5-HT (1B) receptor antagonist. . J Med Chem. 2010 Feb 25;53(4):1876-80.
We describe herein the discovery of novel, de novo designed, 5-HT (1B) receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT (1B) antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT (1B) receptor. |
34(0,1,1,4) |