Structural analysis of chloroquine resistance reversal by imipramine analogs.
For imipramine, desipramine, and eight analogs of these well-known drugs, an N-5-aminoalkyl substitution was a minimum but insufficient structural feature associated with chloroquine resistance reversal. Although a second distal aliphatic nitrogen atom was unnecessary for resistance reversal, the direction of the dipole moment vector was critical.
Bhattacharjee
A K
AK
Department of Medicinal Chemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Kyle
D E
DE
Vennerstrom
J L
JL
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008958:Models, Molecular; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*
D000962:Antimalarials; D002738:Chloroquine; D007099:Imipramine; D003891:Desipramine