8-Aminoquinoline

Drug derivatives

The derivatives primaquine, tafenoquine and pamaquine have been tested for anti-malaria activity. Primaquine is still used routinely worldwide as part of the treatment of Plasmodium vivax and Plasmodium ovale malaria, although how it prevents malarial recurrences is not, at present, clear. Tafenoquine was approved for medical use in Australia and in the United States in 2018. Image:Primaquine.svg|Primaquine Image:Pamaquine.svg|Pamaquine Image:Tafenoquine.svg|Tafenoquine

Directing group

The amine functional group is amenable to formation of amides, and thus can serve as a directing group in organic synthesis.

Preparation

The original synthesis of AQ involved nitration of quinoline to give a mixture of the 5- and 8-nitroderivatives, which were separated by distillation and sublimation. Reduction of the 8-nitro isomer with tin powder in the presence of hydrochloric acid gave the amines. AQ can also be produced by amination of 8-chloroquinoline.

References

References

1. (1997). "X-ray and vibrational studies of 8-aminoquinoline. Evidence for a three-center hydrogen bond". Journal of Physical Organic Chemistry.
2. (2020). "Bidentate Directing Groups: An Efficient Tool in C–H Bond Functionalization Chemistry for the Expedient Construction of C–C Bonds". Chemical Reviews.
3. Sweeney AW. (1 August 2004). "Short report: The activity of pamaquine, an 8-aminoquinoline drug, against sporozoite-induced infections of ''Plasmodium vivax'' (New Guinea strains)". Am J Trop Med Hyg.
4. (2023). "Putative contribution of 8-aminoquinolines to preventing recrudescence of malaria". Tropical Medicine and Infectious Disease.
5. (November 2019). "Guidance for Using Tafenoquine for Prevention and Antirelapse Therapy for Malaria — United States, 2019". MMWR. Morbidity and Mortality Weekly Report.
6. (March 2019). "Clinical utility of tafenoquine in the prevention of relapse of Plasmodium vivax malaria: a review on the mode of action and emerging trial data". Infection and Drug Resistance.
7. (2015). "Bidentate, Monoanionic Auxiliary-Directed Functionalization of Carbon–Hydrogen Bonds". Accounts of Chemical Research.
8. (2013). "8-Aminoquinoline: A Powerful Directing Group in Metal-Catalyzed Direct Functionalization of C-H Bonds". Angewandte Chemie International Edition.
9. (1917). "Über Nitro-amino-chinoline". Berichte der Deutschen Chemischen Gesellschaft.