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N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors.

Research paper by Tjeerd T Barf, Fredrik F Lehmann, Kristin K Hammer, Saba S Haile, Eva E Axen, Carmen C Medina, Jonas J Uppenberg, Stefan S Svensson, Lena L Rondahl, Thomas T Lundbäck

Indexed on: 17 Feb '09Published on: 17 Feb '09Published in: Bioorganic & Medicinal Chemistry Letters



Abstract

Small molecule inhibitors of adipocyte fatty-acid binding protein (A-FABP) have gained renewed interest following the recent publication of pharmacologically beneficial effects of such inhibitors. Despite the potential utility of selective A-FABP inhibitors within the fields of metabolic disease, inflammation and atherosclerosis, there are few examples of useful A-FABP inhibitors in the public domain. Herein, we describe the optimization of N-benzyl-tetrahydrocarbazole derivatives through the use of co-crystal structure guided medicinal chemistry efforts. This led to the identification of a potent and selective class of A-FABP inhibitors as illustrated by N-benzyl-hexahydrocyclohepta[b]indole 30.