Alrestatin

Alrestatin
Names
Preferred IUPAC name
(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetic acid
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
KEGG
UNII
  • 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
  • C1=CC2=C3C(=C1)C(=O)N(C(=O)C3=CC=C2)CC(=O)O
Properties
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).

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in clinical use.[3][4] It is structurally related to tolrestat, another ARI that was briefly marketed before being withdrawn in 1997.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 can be synthesized by the reaction of naphthalic 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