Journal of Medicinal Chemistry, 1971, Vol. 14, N o . 4 283
ANTIMALARIAL 7-CHLOROQUINOLINES
electrostatic binding to a DNA phosphate group. LOSS of correlation found with the parameters associated with the diamino side chain in series 111when series I and 111 were combined suggests that perhaps different substitu-
Antimalarials.
ents at position 7 dictate different drug-DNA orientations which therein alter the manner in which the 4-diamino side chain is able t o interact with the DKA backbone.
7-Chloro-4-(substituted amino)quinolines
TARASINGH,*ROBERT G. STEIN,JOHN F. HOOPS,JOHN H. BIEL,WALLACE I
5
40
Curative; toxic Curative ; toxic>
0.4
Toxic Toxic
40 0 0 4.4 41 40 0 0 .i .8 160 0 0 i.O Active 160 0 0 9.8 ilctive Curative 640 0 ;. Toxic 1 0 640 Numbers refer t o those in Table 1. 11 D , dose in m g / k g ; C, ('\Ires; T D , toxic deaths when mice die 2-5 days port infection, attrihiited to drug toxicity; T - C, increase in mean survival t,ime of the treated mice over the control grtriip. e A coinpd is act,ive if the I' - C exceeds 6.1 days, arid curative if one or more mice live for 60 days or more post infection. 27
3 S HC1 was refluxed with vigorous stirring till the soln became clear (about 1 hr). The mixt was cooled and neutralized with KzC03. The brown oil was extd arid the Et20 ext worked out as usual: bp 86-88' (0.45 mm); yield, 34.0 g (76.4c";). il port,ion was coriverted into the HC1 salt and crystd twice from EtOH, mp 183-18t5'. Anal. (CizHiah'Cl) C, H, X j C1.
Acknowledgment.-This
work was supported by
u.9. Army IIedical Research and Development Coni&-o. DA-49-193mand under the nesearch contract lID-2S69 and iS Contribution S O . 8% from the Army Research Program on Malaria.
