D 24 31 108 43'* Survey Number (see footnote8); the five-digit numbers are DR = drug repository, National Institutes of Health.6 For quinine equivalents see (3). °Refers to analyses listed in Table IV. d Melts with decomposition. * These yields refer to highly purified material. / See experimental section. g Absolute ethanol was used as the reaction solvent. h For the data on the other product isolated from this reaction, see D. *' Yield after one recrystallization. > Yield after several washings with ethanol. * For the data on the other product isolated from this reaction, see C.1 Originally prepared (4c) by heating dibenzoylmethane with excess morpholine; m.p. 96-97°. A mixture melting point of samples prepared in the two ways showed no depression. Acid hydrolysis gave dibenzoylmethane. m Distilled ßmethoxybenzalacetophenone was used as starting material. " Allowed to stand overnight in the refrigerator. p Solubility: in water at 25°, 0.05 g. per 100 ml.; at 90°, 0.1 g. per 100 ml.; in 3 N HC1 at 25°, 1.0 g. per 100 ml.the high antibacterial activity of benzalacetophenone and dibenzoylethylene in mind [cf. (8)].9Absorption spectra of six of these compounds10 over the wavelength range 8 The following tests on substituted chalcones were carried out at the Lilly Research
This investigation had its beginning in the fall of 1942 as a part of the cooperative effort initiated by the Division of Chemotherapy of the National Institute of Health under Dr. L. F. Small (1) and it was continued into the summer of 1944 at which time, although not completed, it was interrupted because of the greater promise and urgency of other problems. It was based on convincing *
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,
This research was a part of an exploratory program on quinine-type synthetic antimalarials.3 The objective was the preparation of some novel a-aryl-|8-dialkylamino ketones and alcohols of the type I, II, XI (and its alcohol), and XVI, involving the furyl group as the central aromatic nuclear system. Early leads had indicated slight activity
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