Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity

Mark Hadden; Allan Goodman; Cheng Guo; Peter R Guzzo; Alan J Henderson; Kevin Pattamana; Megan Ruenz; Bruce J Sargent; Brian Swenson; Larry Yet; Jian Liu; Shuwen He; Iyassu K Sebhat; Linus S Lin; Constantin Tamvakopoulos; Qianping Peng; Yanqing Kan; Oksana Palyha; Theresa M Kelly; Xiao-Ming Guan; Joseph M Metzger; Marc L Reitman; Ravi P Nargund

doi:10.1016/j.bmcl.2010.03.028

Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity

Bioorg Med Chem Lett. 2010 May 1;20(9):2912-5. doi: 10.1016/j.bmcl.2010.03.028. Epub 2010 Mar 12.

Affiliation

¹ AMRI, 26 Corporate Circle, Albany, NY 12212, USA. mark.hadden@amriglobal.com

PMID: 20347296
DOI: 10.1016/j.bmcl.2010.03.028

Abstract

SAR around non-peptidic potent bombesin receptor subtype-3 (BRS-3) agonist lead 2 is presented. Attempts to replace the carboxylic acid with heterocyclic isosteres to improve oral bioavailability and brain penetration are described.

MeSH terms

Administration, Oral
Animals
Anti-Obesity Agents / chemical synthesis*
Anti-Obesity Agents / chemistry
Anti-Obesity Agents / therapeutic use
Brain / metabolism
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / therapeutic use
Mice
Obesity / drug therapy
Rats
Receptors, Bombesin / agonists*
Receptors, Bombesin / metabolism
Structure-Activity Relationship

Substances

Anti-Obesity Agents
Imidazoles
Receptors, Bombesin
bombesin receptor subtype 3