4-N-, 4-S-, and 4-O-chloroquine analogues: influence of side chain length and quinolyl nitrogen p K a on activity vs chloroquine resistant malaria

…, JN Alumasa, K Yearick, KA Ekoue-Kovi…

Index: Natarajan, Jayakumar K.; Alumasa, John N.; Yearick, Kimberly; Ekoue-Kovi, Kekeli A.; Casabianca, Leah B.; De Dios, Angel C.; Wolf, Christian; Roepe, Paul D. Journal of Medicinal Chemistry, 2008 , vol. 51, # 12 p. 3466 - 3479

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Citation Number: 87

Abstract

Using predictions from heme− quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure− function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the p K a of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side ...