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

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Barf T, Lehmann F, Hammer K, Haile S, Axen E, Medina C, Uppenberg J, Svensson S, Rondahl L, Lundback T

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

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1745-8. doi: 10.1016/j.bmcl.2009.01.084. Epub 2009 Jan 30.

PubMed ID
19217286 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
5-(3-carbamoylbenzyl)-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-4-carboxylic acidFatty acid-binding protein, adipocyteIC 50 (nM)450N/AN/ADetails
5-(3-carbamoylbenzyl)-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-4-carboxylic acidFatty acid-binding protein, adipocyteIC 50 (nM)69N/AN/ADetails
9-benzyl-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acidFatty acid-binding protein, adipocyteIC 50 (nM)590N/AN/ADetails