Abstract
Selected for their expected ability to inhibit HIV replication, a series of eight heterodimers containing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and an Integrase Inhibitor (INI), bound by a linker, were designed and synthesized. For the NRTIs, d4U, d2U and d4T were chosen. For the INIs, 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid (6) and 4-(3,5-dibenzyloxyphenyl)-2,4-dioxobutyric acid (9) (belonging to the beta-diketo acids class) were chosen. The conjugation of the two different inhibitors (NRTI and INI) was performed using an amino acid (glycine or beta-alanine) as a cleavable linker.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-HIV Agents / chemical synthesis*
-
Anti-HIV Agents / chemistry
-
Anti-HIV Agents / pharmacology*
-
Cell Line
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
Drug Design
-
Drug Evaluation, Preclinical
-
HIV Integrase Inhibitors / chemical synthesis*
-
HIV Integrase Inhibitors / chemistry
-
HIV Integrase Inhibitors / pharmacology*
-
HIV-1 / drug effects
-
HIV-1 / physiology
-
Humans
-
Leukocytes, Mononuclear / drug effects
-
Microbial Sensitivity Tests
-
Molecular Structure
-
Reverse Transcriptase Inhibitors / chemical synthesis*
-
Reverse Transcriptase Inhibitors / chemistry
-
Reverse Transcriptase Inhibitors / pharmacology*
-
Structure-Activity Relationship
-
Virus Replication / drug effects
Substances
-
Anti-HIV Agents
-
HIV Integrase Inhibitors
-
Reverse Transcriptase Inhibitors