2003
DOI: 10.1021/jm030796n
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Isoquine and Related Amodiaquine Analogues:  A New Generation of Improved 4-Aminoquinoline Antimalarials

Abstract: Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial that can cause adverse side effects including agranulocytosis and liver damage. The observed drug toxicity is believed to involve the formation of an electrophilic metabolite, amodiaquine quinoneimine (AQQI), which can bind to cellular macromolecules and initiate hypersensitivity reactions. We proposed that interchange of the 3' hydroxyl and the 4' Mannich side-chain function of amodiaquine would provide a new series of analogues that cannot form toxic qu… Show more

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Cited by 129 publications
(128 citation statements)
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“…The organic solution was washed with water, dried over anhydrous sodium sulphate and then evaporated to dryness under reduced pressure to yield the crude product. The product was recrystallized from methanol [11,17] .…”
Section: General Procedures Of Synthesismentioning
confidence: 99%
“…The organic solution was washed with water, dried over anhydrous sodium sulphate and then evaporated to dryness under reduced pressure to yield the crude product. The product was recrystallized from methanol [11,17] .…”
Section: General Procedures Of Synthesismentioning
confidence: 99%
“…The resulting molecule isoquine (ISQ 1) 32 (Fig. 13) is more active against the chloroquine resistant K1 strain than amodiaquine 2 [175]. Unfortunately, as with AQ-13 31, the easy access of hydroxylating enzymes to the methylene groups in aposition of the nitrogen atom results in poor bioavailability.…”
Section: Tert-butyl-isoquinementioning
confidence: 99%
“…In contrast to AQ, IQ was excreted primarily as glucuronide, instead of glutathione conjugate. 10 Another promising compound from the class of the 4-aminoquinolines is tebuquine (TQ), which is a biaryl analogue of AQ with a p-chlorophenyl moiety substituted at the 5-position of the 4-hydroxyaniline side chain of AQ. TQ is significantly more active than AQ and CQ in both in vitro and in vivo tests.…”
Section: Introductionmentioning
confidence: 99%
“…In contrast to AQ, IQ was excreted primarily as glucuronide, instead of glutathione conjugate. 10 Another promising compound from the class of the 4-aminoquinolines is tebuquine (TQ), which is a biaryl analogue of AQ …”
mentioning
confidence: 99%