Alrestatin

Alrestatin is an inhibitor of aldose reductase, an enzyme involved in the pathogenesis of complications of diabetes mellitus, including diabetic neuropathy.[1][2]

Alrestatin
Names
Preferred IUPAC name
(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
KEGG
PubChem CID
UNII
InChI
  • InChI=1S/C14H9NO4/c16-11(17)7-15-13(18)9-5-1-3-8-4-2-6-10(12(8)9)14(15)19/h1-6H,7H2,(H,16,17)
    Key: GCUCIFQCGJIRNT-UHFFFAOYSA-N
  • InChI=1/C14H9NO4/c16-11(17)7-15-13(18)9-5-1-3-8-4-2-6-10(12(8)9)14(15)19/h1-6H,7H2,(H,16,17)
    Key: GCUCIFQCGJIRNT-UHFFFAOYAQ
SMILES
  • C1=CC2=C3C(=C1)C(=O)N(C(=O)C3=CC=C2)CC(=O)O
Properties
Chemical formula
 C14H9NO4
Molar mass 255.229 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

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in clinical use.[3][4] It is structurally related to tolrestat, another ARI that was briefly marketed before being withdrawn in 1997.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 can be synthesized by the reaction of 1,8-naphthoic anhydride with glycine.[5]

Alrestatin synthesis

See also

References
  1. 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.
  2. 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.
  3. 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.
  4. Veves, Aristidis (2007). "Aldose reductase inhibitors for the treatment of diabetic neuropathy". In Rayaz A., Malik; Veves, Aristidis (eds.). Diabetic Neuropathy: Clinical Management. Totowa, NJ: Humana Press. pp. 309–11. ISBN 978-1-59745-311-0. Retrieved 2013-02-13.
  5. Ayerst Mckenna & Harrison, U.S. Patent 3,821,383
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