Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3) based on an omeprazole lead

David L Carlton; Lissa J Collin-Smith; Alejandro J Daniels; David N Deaton; Aaron S Goetz; Christopher P Laudeman; Thomas R Littleton; David L Musso; Ronda J Ott Morgan; Jerzy R Szewczyk; Cunyu Zhang

doi:10.1016/j.bmcl.2008.09.033

Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3) based on an omeprazole lead

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5451-5. doi: 10.1016/j.bmcl.2008.09.033. Epub 2008 Sep 11.

Authors

David L Carlton¹, Lissa J Collin-Smith, Alejandro J Daniels, David N Deaton, Aaron S Goetz, Christopher P Laudeman, Thomas R Littleton, David L Musso, Ronda J Ott Morgan, Jerzy R Szewczyk, Cunyu Zhang

Affiliation

¹ Department of Pharmaceutical Development, Physical Properties and Developability, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.

PMID: 18818070
DOI: 10.1016/j.bmcl.2008.09.033

Abstract

Starting from a weak omeprazole screening hit, replacement of the pyridine with a 1,3-benzodioxole moiety, modification of the thioether linkage, and substitution of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3 agonists.

MeSH terms

Baculoviridae / metabolism
Benzimidazoles / chemistry
Brain / metabolism
Chemistry, Pharmaceutical / methods
Chlorofluorocarbons, Methane / chemistry
Drug Design
Drug Evaluation, Preclinical
Humans
Kinetics
Models, Chemical
Omeprazole / chemistry*
Pyridines / chemistry
Receptors, Bombesin / agonists*
Receptors, Bombesin / chemistry
Sulfides / chemistry

Substances

Benzimidazoles
Chlorofluorocarbons, Methane
Pyridines
Receptors, Bombesin
Sulfides
bombesin receptor subtype 3
benzimidazole
Omeprazole
fluoroform