Synthesis of Ring‐Substituted 4‐Aminoquinolines and Evaluation of Their Antimalarial Activities.

Abstract

The substitution effects in the B-ring of 4-hydroxyquinoline on antimalarial activity against drug-resistant parasite strains are investigated. The key steps in the synthesis of libraries (VIII) and (X) consist of and addition-elimination reaction to afford the ene-amine precursor (IV) and the subsequent microwave-assisted cyclization step. Compounds with the shorter side chain, cf. (VIII), are consistently more potent, especially against the drug-resistant W2 strain. The most active compounds possess substituents at either the 6-or 7-position on the quinoline ring. In general, small electron-withdrawing groups yield active substitutions. -(MADRID, P. B.; SHERRILL, J.; LIOU, A. P.; WEISMAN, J. L.; DERISI, J. L.; GUY*, R. K.; Bioorg. Med. Chem. Lett. 15 (2005) 4, 1015-1018; Dep. Pharm. Chem., Sch. Pharm., Univ. Calif., San Francisco, CA 94143, USA; Eng.) -H. Hoennerscheid 25-144

Design and synthesis of chloroquine analogs with anti-breast cancer property

“…Compounds derived from bioisoteric replacement of 7-chloro group with 7-trifluoromethyl substitution on the 4-aminoquinoline ring system having diethyl (20), pyrrolidinyl (21), piperidinyl (22), It may be important to note that the substitution of the 4-(7-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl ring system on 4-aminoquinoline lateral side chain is very effective in differential antiproliferation on cancer cells when the 7th position of the ring is a eCl group (14), but not eCF 3 group (27). Conversely, the substitution of the 4-(7-chloroquine 4-yl)piperazin-1-yl ring system on 4-aminoquinoline lateral side chain showed higher differential antiproliferation effects on cancer cells when the 7th position of the ring is a eCF 3 group (26) than a eCl group (13).…”

Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum

“…13,14 In the context of exploring the 9-aminoacridine scaffold of quinacrine (3) to target the propagation of prions, 15-17 we became interested in re-evaluating this class of molecules for anti-malarial activity, particularly against CRPF. Herein we report a parallel synthetic strategy to generate libraries of 9-aminoacridines based on the general structure of quinacrine, along with in vitro cell-based screening results against drug-sensitive and drug-resistant strains of P. falciparum.…”

Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography–high‐resolution mass spectrometry in combination with multiple data‐mining tools in tandem

“…Decreased activity has been found for 4‐amino‐quinoline antimalarials after replacement of the 7‐chloro group either by an electron‐donor group like NH 2 or by an electron‐withdrawing group like NO 2 (Egan et al , ; Kaschula et al , ; Madrid et al , ). The six metabolites of PQ found in this study were expected to keep the antimalarial activity.…”