Alrestatin
 | |
| Names | |
|---|---|
| IUPAC name
(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid | |
| Identifiers | |
| 51876-97-2 | |
| ChEMBL | ChEMBL63055 |
| ChemSpider | 2036 |
| |
| Jmol-3D images | Image |
| PubChem | 2120 |
| |
| Properties | |
| C14H9NO4 | |
| Molar mass | 255.226 |
| Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa) | |
| Infobox references | |
Alrestatin is an inhibitor of aldose reductase, an enzyme involved in the pathogenesis of complications of diabetes mellitus, including diabetic neuropathy.[1][2]
Alrestat was first synthesized in 1969 and was the first aldose reductase inhibitor (ARI) with oral bioavailability to undergo clinical trials, in the late 1970s and early 1980s. Low-quality trials and a high incidence of adverse effects (particularly hepatotoxicity) led to termination of its development, and it was never in clinical use.[3][4] It is structurally related to tolrestat, another ARI that was briefly marketed before being withdrawn in 1997.
Synthesis
Alrestatin synthesis: Ayerst Mckenna & Harrison, U.S. Patent 3,821,383
Napactidine
Napactidine synthesis: U.S. Patent 3,903,163.
- Triethyloxonium tetrafluoroborate aka Meerwein's reagent.
Naftidine
Naftidine synthesis: DE 2,716,943.
References
- ↑ Gabbay KH, Spack N, Loo S, Hirsch HJ, Ackil AA (April 1979). "Aldose reductase inhibition: studies with alrestatin". Metab Clin Exp 28 (4 Suppl 1): 471–6. doi:10.1016/0026-0495(79)90059-3. PMID 122298.
- ↑ Ehrig T, Bohren KM, Prendergast FG, Gabbay KH (June 1994). "Mechanism of aldose reductase inhibition: binding of NADP+/NADPH and alrestatin-like inhibitors". Biochemistry 33 (23): 7157–65. doi:10.1021/bi00189a019. PMID 8003482.
- ↑ Striker, Gary E.; Gueriguian, John L. (1991). Diabetic complications: epidemiology and pathogenetic mechanisms. New York: Raven Press. pp. 293–4. ISBN 0-88167-648-9.
- ↑ Veves, Aristidis (2007). "Aldose reductase inhibitors for the treatment of diabetic neuropathy". In Rayaz A., Malik; Veves, Aristidis. Diabetic Neuropathy: Clinical Management. Totowa, NJ: Humana Press. pp. 309–11. ISBN 1-59745-311-0. Retrieved 2013-02-13.