Aldose reductase inhibitors structure

Aldose reductase inhibitors Structure-activity relationships and therapeutic potential, 18, 139 Alzheimer s Disease A pharmacological challenge, 25, 203 Amantadine, 8, 11... 

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. 

Morikawa, T. Kishi, A. Pongpiriyadacha, Y. Matsuda, H. Yoshikawa, M. Structures of new friedelane-type triterpenes and eudesmane-type sesquiterpene and aldose reductase inhibitors from Salacia chinensis. J. Nat. Prod. 2003, 66, 1191-1196. 

Matsuda H, Nishida N, Yoshikawa M. (2002) Antidiabetic principles of natural medicines. V. Aldose reductase inhibitors from Myrcia multiflora DC. (2) structures of Myrciacitrins IB, IV, and V. Chem PharmBull 50 429 31. 

Three aldose reductase inhibitors (490 492) were isolated from Dictyodendrilla sp. from Japan and their structures were determined by X-ray analysis and spectroscopic studies [418],... 

Fig. 23 Structures of epatrestat, zopolrestat, 2,4-dioxo-5-(naphthylmethylene)-3-thiazol-idineacetic acid (a) and its 2-thioxo analogue (b) as Aldose Reductase inhibitors...

Klopman, G. and Buyukbingol, E. (1988). An Artificial Intelligence Approach to the Study of the Structural Moieties Relevant to Drug-Receptor Interactions in Aldose Reductase Inhibitors. Mol.Pharm., 34,852-862. 

Fig. 29. Chemical structure of some aldose reductase inhibitors.

Sun W, Oates PJ, Coutcher JB, Gerhardinger C, Lorenzi M. A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormabties in experimental diabetic retinopathy. Diabetes 2006 55 2757-2762. 

Yoshikawa M, Shimada H, Nishida N, Li Y, Toguchida I, Yamahara J, Matsuda H. (1998) Antidiabetic principles of natural medicines. II. Aldose reductase and a-glucosidase inhibitors from Brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtacae) Structures of myrciacitrins I and II and myrciaphenones A and B. Chem Pharm Bull 46 113-119. 

Aldose reductase (ALR2 EC 1.1.1.21) is an 36 kDa enzyme that catalyzes the reduction of a wide range of carbonyl-containing compounds to their corresponding alcohols. It is a member of an extensive aldo-keto oxidoreductase enzyme family, a collection of structurally similar proteins expressed in both animals and plants. Most members of the enzyme family possess similarities in molecular mass, pH optimum, coenzyme dependence, and demonstrate overlapping specificity for many substrates and inhibitors. 

Wilson DK, Tarle I, Petrash JM, Quiocho FA. Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat. Proc Natl Acad Sci USA 1993 90 9847-9851. 

In 1982 Ayerst Laboratories in Montreal became the first company in Canada to install a commercial software tool (the SYBYL suite from Tripos Associates) to help in the development of pharmacophoric models from structure-activity relationships. The installation of the software was the second ever, worldwide, by a company and is a testimonial to the foresight of the director of medicinal chemistry, Dr. Leslie Humber, for having championed its installation. Dr. Adi M. Treasurywala, then an organic chemist with some experience in medicinal chemistry, became the first industrial computational chemist in Canada that year. The use of modeling approaches contributed in a minor but significant way to the discovery of the compound known as Tolrestat, which was an inhibitor of lens aldose reductase. This led to the acknowledgment of Treasurywala as a coinventor of the drug on several patents that were filed in this research area. Approximately in 1983, Ayerst closed down its discovery effort in Canada and moved to Princeton, New Jersey, where an expanded effort in the area of computational chemistry continues. 

Some typical structural templates embedded with the thiazoHdine frame have been reported as potent inhibitors of aldose reductase (AR), an enzyme in the polyol pathway responsible for the conversion of glucose to sorbitol. In this, the accumulation of sorbitol has been attributed to causing cataracts, neuropathy, and retinopathy in diabetic cases [ 157,158]. The planar hydrophobic (aromatic) regions and propensity to charge transfer interactions have been... 

The structure of (60) and other inhibitors Tound to porcine aldose reductase (136) provided a rich lode of information on the requirements for potent and selective inhibition of aldose reductase. This was mined by scientists at the Institute for Diabetes Discovery, in a project that began in 1996. The Institute for Diabetes Discovery filed an IND application for (61) (lidorestat, IDD 676), a potent aldose... 

Amic, D., Davidovic-Amic, D., Beslo, D., Lucic, B. and Trinajstic, N. (1997). The Use of the Ordered Orthogonalized Multivariate Linear Regression in a Structure-Activity Study of Cou-marin and Flavonoid Derivatives as Inhibitors of Aldose Reductase. J.Chem.Inf.Comput.ScL, 37,581-586. 

The inhibitory activities of 1 l-oxopyrido[2,l-i>]quinazolinecarboxylic acids on rat lens and human placental aldose reductase were studied. From the specific structural and electronic similarities of diverse aldose reductate inhibitors the pharmacophor requirements for an inhibitor were postulated. ... 

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