Structure based evolution of a novel series of positive modulators of the AMPA receptor

Craig Jamieson; John K F Maclean; Christopher I Brown; Robert A Campbell; Kevin J Gillen; Jonathan Gillespie; Bert Kazemier; Michael Kiczun; Yvonne Lamont; Amanda J Lyons; Elizabeth M Moir; John A Morrow; John Pantling; Zoran Rankovic; Lynn Smith

doi:10.1016/j.bmcl.2010.11.098

Structure based evolution of a novel series of positive modulators of the AMPA receptor

Bioorg Med Chem Lett. 2011 Jan 15;21(2):805-11. doi: 10.1016/j.bmcl.2010.11.098. Epub 2010 Nov 25.

Authors

Craig Jamieson¹, John K F Maclean, Christopher I Brown, Robert A Campbell, Kevin J Gillen, Jonathan Gillespie, Bert Kazemier, Michael Kiczun, Yvonne Lamont, Amanda J Lyons, Elizabeth M Moir, John A Morrow, John Pantling, Zoran Rankovic, Lynn Smith

Affiliation

¹ Merck Research Laboratories, MSD, Newhouse, Motherwell, Lanarkshire ML1 5SH, UK. craig.jamieson@strath.ac.uk

PMID: 21190850
DOI: 10.1016/j.bmcl.2010.11.098

Abstract

Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19.

MeSH terms

Allosteric Regulation
Animals
Cell Line
Crystallography, X-Ray
Drug Design*
Humans
Indans / chemistry*
Indans / metabolism
Indans / pharmacokinetics
Indans / pharmacology*
Microsomes, Liver / metabolism
Models, Molecular
Nervous System Diseases / drug therapy
Nervous System Diseases / metabolism
Pyrazoles / chemistry
Pyrazoles / metabolism
Pyrazoles / pharmacokinetics
Pyrazoles / pharmacology
Rats
Rats, Wistar
Receptors, AMPA / metabolism*
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / metabolism
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology*

Substances

Indans
Pyrazoles
Receptors, AMPA
Sulfonamides