2. Academic Validation
  3. Highly potent, non-basic 5-HT6 ligands. Site mutagenesis evidence for a second binding mode at 5-HT6 for antagonism

Highly potent, non-basic 5-HT6 ligands. Site mutagenesis evidence for a second binding mode at 5-HT6 for antagonism

  • Bioorg Med Chem Lett. 2010 Jun 1;20(11):3436-40. doi: 10.1016/j.bmcl.2010.03.110.
Ralph N Harris 3rd 1,  Russel S Stabler,  David B Repke,  James M Kress,  Keith A Walker,  Renee S Martin,  Julie M Brothers,  Mariola Ilnicka,  Simon W Lee,  Tara Mirzadegan
Affiliations

Affiliation

  • 1 Roche Palo Alto LLC, 3431 Hillview Ave., Palo Alto, CA 94304, USA.
PMID: 20434910 DOI: 10.1016/j.bmcl.2010.03.110
Abstract

A series of 5-HT(6) ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure-activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new alternative binding mode to 5-HT(6) for antagonism.

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