A series of mono-, di-, tri-, and tetrasubstituted 9-phenanthrene amino alcohols has been prepd in which each compd bears at least one CF3 group. A number of these compds, triand tetrasubstituted with a combination of CF3 and Cl groups, are the most active, nontoxic amino alcohols to emerge from the vast primary screen {Plasmodium berghei, mouse) of the Army's Research Program on Malaria. The most effective member of the series, 6,7-dichloro-2,4-bis(trifluoromethyl)-a-(di-n-propylaminomethyl)-9-phenanthrenemethanoTHCl (159), is 100% curative at 5 mg/kg and active at concentrations as low as 1.25 mg/kg. Antimalarial enhancement of 9-phenanthrenemethanols by introduction of CF3 groups or a combination of CF3 and halogen was described earlier.1 In an effort to approach the optimal substitution pattern for this series we have synthesized the compds included in Table I.Chemistry. The preparative routes were essentially those described in paper 1,1 Details have been tabulated in the Experimental Section.

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t I n this case suffix ' a ' means the corresponding optically active compounds, and this sign is used in the following coinpounds.Chao Tse-yuan, Chou Yun-lee, Young Tao-tsin, and Chou Tsenquo, Scientica Sinica, 1962, 11, 215.2 Pan Pei-chuan, Chou Yun-lee, Sun Tsun-tsi, and Yee-sheng,

A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered.