Download MendeleyDesign and synthesis of selective, dual fatty acid binding protein 4 and 5 inhibitors.
Kuhne, H., Obst-Sander, U., Kuhn, B., Conte, A., Ceccarelli, S.M., Neidhart, W., Rudolph, M.G., Ottaviani, G., Gasser, R., So, S.S., Li, S., Zhang, X., Gao, L., Myers, M.(2016) Bioorg Med Chem Lett 26: 5092-5097
- PubMed: 27658368
- DOI: https://doi.org/10.1016/j.bmcl.2016.08.071
- Primary Citation of Related Structures:
5HZ5, 5HZ6, 5HZ8, 5HZ9 - PubMed Abstract:
Dual inhibition of fatty acid binding proteins 4 and 5 (FABP4 and FABP5) is expected to provide beneficial effects on a number of metabolic parameters such as insulin sensitivity and blood glucose levels and should protect against atherosclerosis. Starting from a FABP4 selective focused screening hit, biostructure information was used to modulate the selectivity profile in the desired way and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. With very good pharmacokinetic properties and no major safety alerts, compound 12 was identified as a suitable tool compound for further in vivo investigations.
Organizational Affiliation:
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland. Electronic address: [email protected].
