Antimarlarials. Substituted 2-phenyl-4-quinolinemethanols

Abstract

Twenty-six new CY-( alkglaminomethyl)-2-phenyl-4-quinolinemethanols have been synthesized for evaluation of their antimalarial activity. Kine new 2-phenylcinchoninic acids were prepared together with the several intermediates leading to the amino alcohols. An anomalous orientation effect of methoxy substitution in the anilines used in the Doebner reaction for the preparation of cinchoniriic acids was noted. In the environment of the Doebner reaction the methoxy group became a meta-directing group rather than ortho,para directing. The position of the methoxy substitution in the 2-phenyl-4-quinolinemethanols prepared influenced the basicity of the quinoline nitrogen. The heterocyclic nitrogen in 2-(4-methoxyphenyl)-and 7-methoxy-2-phenyl-substituted 4-quinolinemethanols was seemingly equivalent in base strength to the aliphatic tertiary nitrogen in the amino alcohol side chain in contrast to similar compounds in which there was chloro substitution in these positions. Twenty of the compounds have been tested for antimalarial activity toward Plasmodium berghei in mice. Single doses of from 40 to 640 mg/kg prolonged the life of infected mice to at least 30 days, whereas the survival time of controls was 7.0 f 0.5 days. The one dioctylamino derivative was inactive a t a dose of 640 mg/kg. The diethylamino-1-methylbutylamino derivative was toxic a t a dose of 40 mg/kg. The compounds were phototoxic to albino mice a t dosage levels from 5 to 400 mg/kg. ( I ? ) A . 1, \ViI~ls, Ow. Reaclzons, 2, 107 (lW4). Jlay 196s ANTIMALARIAL 2-PHE,hjYL-4-61UINoLl~~M~~l~HANOL8 429 -----A -COCl Reaction Yield,

Photosensitized Lysis of Red Blood Cells by Phototoxic Antimalarial Compounds

“…Chloroquine diphosphate and quinacrine dihydrochloride were obtained from Aldrich (Milwaukee, WI). The remaining antimalarials were synthesized as previously described (Gillespie et al, 1968;Lutz ef al., 1946). Phosphate buffered saline was supplied by GIBCO (Gaithersburg.…”

Approaches to a photocleavable protecting group for alcohols

“…14 It is noted that previous studies reported successful synthetic pathways to quinoline methanols (compound 2, Scheme 1). 15,16 A family of compounds was prepared to test whether photocleavage of this group would proceed with ultraviolet light (350 nm) in good yields. The alcohols examined included one compound (4e), which would likely be destroyed under strong oxidizing or reducing conditions.…”

Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors

“…Some nitro compounds 47, 51, 55, and 57 were prepared by regioselective mononitration of 29, 42, 32, and 34 with sodium nitrate in sulfuric acid, respectively. Catalytic reduction (H2/Pd black) or metal and acid reduction (SnCl2/HCl) of the nitro group in 34 and 55 furnished anilines 35 and 56 in good yields. Phenol 37 was prepared from methyl ether 36 by reaction with 48% hydrobromic acid (HBr) at 130 °C.…”