A series of 2-substituted analogues of the exceptional drug 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3- (trifluoromethyl)phenoxy]quinoline (I) were prepared and evaluated for both suppressive and prophylactic antimalarial activity. The preparation of analogues of compound I was of interest due to the high level of both blood and tissue schizonticidal activity demonstrated by this compound. One analogue, 8a, was found to be both more active and less toxic than the parent compound I. In addition, three analogues of example 8a were prepared. Although two of the three analogues showed significant antimalarial activity, both were inferior to compound 8a.

A series of 27 hydantoins was prepared and tested as antitumor agents. These were variously substituted in the 5 position but with special emphasis on the substituents (chloro, acetyl, chloroacetyl, and methyl) in the 1 and/or 3 positions. The most active compound was 5,5-bis(4-chlorophenyl)-1,3-dichlorohydantoin with a T/C value of 190% against P-388 lymphocytic leukemia in mice.

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.

Hydrolysis of cis-N-(2-p-Toluamido-1,2-di-p-tolylethenyl)toluamide.-Amide 7b (54 mg, 1.1 mmol) was hydrolyzed, in an identical manner with amide 7a, affording p-toluic acid, mp 177-180°, and 24 mg (91%) of 2,4,5-tris-p-tolyloxazole, which was recrystallized from absolute ethanol, mp 143-145°( lit.24 mp 145°).Pyrolysis of a's-A''-(2-p-Toluamido-l,2-di-p-tolylethenyl)toluamide.-Amide 7a (200 mg, 0.43 mmol) was py roly zed, in an identical manner with amide 7a, affording a distillate (p-tolunitrile, p-toluic acid, and p-toluic acid anhydride) and a residue, which was recrystallized from ethanol giving 130 mg (90%) of 2,4,5-tris-p-tolylimidazole, mp 232-233°. Each compound was substantiated by spectral comparisons with authentic samples.

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