Aldose reductase inhibitors design

Iwata Y, Arisawa M, Hamada R, Kita Y, Mizutani MY, Tomioka N, Itai A, Miyamoto S. Discovery of novel aldose reductase inhibitors using a protein structure-based approach 3D-database search followed by design and synthesis. J Med Chem 2001 44 1718-28. 

Pfeifer MA, Schumer MP, Gelber DA. Aldose reductase inhibitors the end of an era or the need for different trial designs Diabetes. 1997 46(suppl 2) S82-S89. 

K.D., Kim, S.H., Kim, J.H., Park, H.J. Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D... 

Howard, E. 1., Sanishvili, R., Cachau, R. E., Mitschler, A., Chevrier, B., Barth, R, Lamour, V., Van Zandt, M., Sibley, E., Bon, C., Moras, D., Schneider, T. R., Joachimiak, A., Podjarny, A. Ultrahigh resolution drug design 1 details of interactions in human aldose reductase-inhibitor complex at 0.66 A. Proteins Struct. Fund. Bioinf. 2004,55, 792-804. 

Rastelli, G., Vianello, P., Barlocco, D., Costantino, L., et al. (1997) Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase. Bioorg. Med. Chem. Lett. 1 1897-1902. 

Polyol Pathway. Recently, theories and data have been emerging which implicate aldose reductase (AR), increased flux through the polyol pathway due to hyperglycemia and accumulation of sorbitol and fructose in the pathophysiology of diabetic complications. The biological rationale and chemical progress towards design of AR inhibitors constitute the major focus of this review. 

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