Antimalarials. 14. 5-(Aryloxy)-4-methylprimaquine analogs. A highly effective series of blood and tissue schizonticidal agents

Abstract

A series of five 5-(aryloxy)-4-methylprimaquine analogues has been prepared and evaluated for antimalarial activity. The compounds were tested for suppressive activity against Plasmodium berghei in mice and for radical curative activity against Plasmodium cynomolgi in the rhesus monkey. The compounds were not only significantly superior to primaquine as radical curative agents but also were suprisingly highly effective as suppressive agents.

Antimalarial activity and inhibition of monoamine oxidases A and B by exo‐erythrocytic antimalarials

“…Comparison of the optical isomers 1A and 1B of primaquine, favouring here the (-) isomer 1B as the less toxic compound, is offset by earlier reports showing that the (+) isomer 1A had a better therapeutic index in rhesus monkeys [16], with both 1A and 1B similarly inhibiting drug metabolism [17]. In view of the appearance of new and much improved antimalarials for radical cure and clearing of tissue parasites, such as 4 [12] or its 4-methyl-substituted analogues [18], further development of either (-)-primaquine (1B) or its (+) isomer 1A does in our opinion not seem warranted. However, the question regarding differences in activity and toxicity of optical isomers of the new generation of analogues should be pursued.…”

Primaquine revisited six decades after its discovery

“…This produced almost 200 PQ derivatives (Tables 2-4) bearing diverse groups in one or more given positions of the ring [6,46,[161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179]. Globally, the most favourable substituent insertions towards anti-malarial activity where those of methyl groups at positions 4 and 2, tert-butyl at position 2, simultaneous insertion of ethyl substituents at positions 2 and 4 and pentyloxy at position 5, as well as insertion at position 5 of alkoxy, fluoro, and 3-or 4-substituted phenoxy groups [51,163].…”

Protection of retinal cells from ischemia by a novel gap junction inhibitor

“…Consequently, we synthesized this class of quinolines and determined their ability to inhibit gap junction dye transfer. PQ1 was synthesized via a modification of the reported protocol [25][26][27] starting from 4-acetaminoanisole. The detailed synthesis is described in Ref.…”

“…After screening several classes of molecules, we focused on substituted quinolines based on their relative binding constants and bioactivities. Primaquine 1 (PQ1) analogs were synthesized via a modification of the reported protocol [25][26][27] starting from 4-acetaminoanisole [27]. The succinic acid salt of PQ1 (structure shown in Fig.…”