Exploration of the effects of linker chain modifications on anti-HIV activities in a series of cosalane analogues.
The effects of linker chain modifications were investigated in a series of cosalane analogues. The modifications investigated included: (1) shortening the three-carbon linker chain between the dichlorodisalicylmethane and the cholestane moiety by one carbon atom; (2) lengthening the linker chain by one carbon; (3) hydrogenation of the double bond in the linker chain; (4) changing the point of attachment of the linker chain from C-3 to C-6; (5) insertion of a phosphate between the steroid and the linker chain. With the exception of the phosphate modification, which abolished anti-HIV activity and increased cytotoxicity, the linker chain modifications produced relatively minor changes in anti-HIV activity and increased cytotoxicity, the linker chain modifications produced relatively minor changes in anti-HIV potency. The steroid and attached linker chain of cosalane therefore appear only to provide a general lipophilic appendage for the dichlorodisalicylmethane pharmacophore.
Golebiewski
W M
WM
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Keyes
R F
RF
Cushman
M
M
D019380:Anti-HIV Agents / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D001312:Aurintricarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D010766:Phosphorylation; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D000998:Antiviral Agents; C083060:cosalane; D001312:Aurintricarboxylic Acid