8 The Medicinal Chemistry of Aldose Reductase Inhibitors

Humber, Leslie G.

doi:10.1016/s0079-6468(08)70425-9

Cited by 37 publications

(29 citation statements)

References 67 publications

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“…These studies provide useful informations on the interactions between these inhibitors and the active site of the enzyme. Extensive work in the field of aldose reductase inhibitors has yielded to a large number of inhibitors for the enzyme belonging to various structural families [25,26]. A set of fifteen aldose reductase inhibitors tested against rat lens and with binding affinities ranging from 4 nm to 2.2 µM was selected from literature [21].…”

Section: Generating and Using Feature-based Pharmacophores For The Almentioning

confidence: 99%

Virtual Screening An Effective Tool for Lead Structure Discovery

Langer¹,

Hoffmann

2001

CPD

122

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Different methods of virtual screening as a tool for lead structure discovery are described. They range from structure based docking procedures to ligand based methods such as the chemical features based pharmacophore hypothesis approach. A review on several successful applications of virtual screening is given. Different approaches have been described to derive pharmacophore models, which were subsequently used for 3D database searching. The studies so far published cover a wide range of pharmacological applications. The results hereby obtained clearly indicate that focused assessment of corporate databases by virtual screening using well validated pharmacophore models yield to a significant improvement in lead structure determination compared to high throughput screening.

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Section: Generating and Using Feature-based Pharmacophores For The Almentioning

confidence: 99%

Virtual Screening An Effective Tool for Lead Structure Discovery

Langer¹,

Hoffmann

2001

CPD

122

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“…16 This compound was synthesized in consideration of the hydrolysis-resistance of an active compound found by screening focused on carboxylic acids. 17 Tolrestat 18 was developed from alrestatin by means of molecular modification, where the imido ring was cleaved to afford naphthoylglycine derivatives. 17,18 Epalrestat was developed by introducing of the substituent onto the 5-position in rhodanine-N-acetic acid.…”

Section: Structures and In Vitro Activities Of Potent Inhibitorsmentioning

confidence: 99%

“…17 Tolrestat 18 was developed from alrestatin by means of molecular modification, where the imido ring was cleaved to afford naphthoylglycine derivatives. 17,18 Epalrestat was developed by introducing of the substituent onto the 5-position in rhodanine-N-acetic acid. 19 The isomeric form of epalrestat has been revealed by X-ray crystal analysis; however, epalrestat easily isomerizes in solution even under natural light.…”

Section: Structures and In Vitro Activities Of Potent Inhibitorsmentioning

confidence: 99%

Aldose Reductase Inhibitors

Oka

Kato

2001

Journal of Enzyme Inhibition

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Aldose reductase ([EC1.1.1.21]: AR) acts on the first step of the polyol metabolic pathway to catalyze the reduction of glucose to sorbitol with NADPH as a coenzyme. Hyperactivity of the pathway in individuals with high blood glucose level is closely related to the onset or progression of diabetic complications. AR inhibitors have therefore been noted as possible pharmacotherapeutic agents for the treatment of diabetic complications. One AR inhibitor has been on the market in Japan, while some potent inhibitors are in clinical trials. Reviewed are the physiological roles of AR, the chemical structures of AR inhibitors, interactions of AR inhibitors with AR using X-ray studies, and the following potencies of AR inhibitors: in vitro activities for AR, in vitro selectivities between AR and aldehyde reductase, their pharmacological effects in vivo, and their effectiveness in clinical trials. Also discussed are directions for the design of future AR inhibitors.

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“…Hydantointype inhibitors have a risk of Steven-Johnson syndrome and hypersensitivity reaction (Pitts et al, 1986;Spielberg et al, 1991). On the other hand, many carboxylic acid derivatives have also been withdrawn from clinical trials due to lack of efficacy or toxicity (Sarges, 1989;Humber, 1987). The carboxylic acid derivatives, Tolrestat and Epalrestat, are the two most effective AR inhibitors, with no serious side effects, and they are approved for marketing in several countries.…”

Section: Introductionmentioning

confidence: 99%

Antihyperglycaemic and aldose reductase inhibitory potential of Acacia catechu hard wood and Tectona grandis leaves

Bhatia

Srivastava

et al. 2010

Med Chem Res

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The ethanolic extract of Acacia catechu hard wood (Ac) and the ethanolic as well as aqueous extracts of Tectona grandis leaves (Tg) showed marked antihyperglycaemic activity in both normoglycaemic and streptozotocininduced diabetic rats at 250 mg/kg dose levels. The ethanolic and aqueous extracts of Ac and Tg also showed marked inhibition on AR from eye lens of normal rats with IC 50 values of 9.30 and 9.08 and 3.05, 4.51 lg/ml, respectively. The ethanolic as well as aqueous extracts of both Ac and Tg also showed marked inhibition on AR from eye lens of STZinduced diabetic rats with IC 50 values of 4.70 and 4.91 and 4.71 and 4.83 lg/ml. These results suggest that Acacia catechu hard wood and Tectona grandis leaves could be a new approach in the development of therapeutic or preventive agents for diabetic late-stage complications.

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8 The Medicinal Chemistry of Aldose Reductase Inhibitors

Cited by 37 publications

References 67 publications

Virtual Screening An Effective Tool for Lead Structure Discovery

Virtual Screening An Effective Tool for Lead Structure Discovery

Aldose Reductase Inhibitors

Antihyperglycaemic and aldose reductase inhibitory potential of Acacia catechu hard wood and Tectona grandis leaves

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