Antimalarial activity of some novel derivatives of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (pyrimethamine).

Thirteen new analogs of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (Daraprim, pyrimethamine) in which the alph position of the 6-ethyl substituent was modified were prepared. The respective oxygens analogs (ketals, ketone, alcohol), the dimethyl hydrazone, and the nitrone displayed activities in the range of 1/4 to 1/16 that of pyrimethamine toward Plasmodium berghei in mice. The therapeutic ratios of some of these compounds may be slightly better than that of pyrimethamine.