3FR4

N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte Fatty-Acid Binding Protein (A-FABP) inhibitors

Summary for 3FR4

• Entry DOI: 10.2210/pdb3fr4/pdb
• Related: 3FR2 3FR5
• Descriptor: Fatty acid-binding protein, adipocyte, 9-[2-(trifluoromethyl)benzyl]-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (3 entities in total)
• Functional Keywords: selective adipocyte fatty-acid binding protein (a-fabp) inhibitors, cytoplasm, lipid-binding, nucleus, phosphoprotein, polymorphism, transport, lipid binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15090
• Total number of polymer chains: 1
• Total formula weight: 15113.27

Authors

Barf, T.,Hammer, K.,Lehmann, F.,Haile, S.,Axen, E.,Medina, C.,Uppenberg, J.,Svensson, S.,Rondahl, L.,Lundb ck, T. (deposition date: 2009-01-08, release date: 2009-03-10, Last modification date: 2024-02-21)

Primary citation

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., 19:1745-1748, 2009

PubMed 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.

PubMed: 19217286
DOI: 10.1016/j.bmcl.2009.01.084

Experimental method

X-RAY DIFFRACTION (2.16 Å)