ABSTRACT
A series of 2',3'-didehydro-2',3'-dideoxynucleosides substituted with an alkynylhydroxy- (6, 7, 12 and 13) and alkynylamino- (20) groups at the C-5 position were synthesized. All these five target modified nucleosides were tested for anti-human immunodeficiency virus type 1 activity in CEM-SS and MT-4 cells and unfortunately displayed no improvement in antiviral activity.
Subject(s)
Alkynes/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacology , Stavudine , Anti-HIV Agents/chemistry , Cell Line , Cell Line, Tumor , Drug Evaluation, Preclinical , HIV-1/drug effects , HIV-1/physiology , Humans , Microbial Sensitivity Tests , Molecular Structure , Reverse Transcriptase Inhibitors/chemistry , Stavudine/analogs & derivatives , Stavudine/chemical synthesis , Stavudine/pharmacology , Structure-Activity Relationship , Virus Replication/drug effectsABSTRACT
Expected for the ability to inhibit HIV replication, we report the synthesis of two heterodimers of the general formula: [2NRTI]-C5-GLY-SUCCINYL-Npiperazinyl-[NNRTI] (18, 19) containing both a Nucleoside Reverse Transcriptase Inhibitor (10, 11) and a Non-Nucleoside Reverse Transcriptase Inhibitor (8) [Trovirdine Analogue belonging of the phenethyl thiazolyl thiourea class] connected through the "succinyl-glycine" spontaneously cleavable linker.
Subject(s)
HIV-1/physiology , Reverse Transcriptase Inhibitors/chemical synthesis , Virus Replication/drug effects , Dimerization , HIV-1/drug effects , Indicators and Reagents , Models, Molecular , Molecular Structure , Pyridines/chemistry , Reverse Transcriptase Inhibitors/pharmacologyABSTRACT
A series of eleven heterodimers containing both a nucleoside analogue (d4U, d4T) and a non-nucleoside type inhibitor (Trovirdine analogue) were synthesized and evaluated for their ability to inhibit HIV replication. Unfortunately, the (N-3)d4U-Trovirdine conjugates (9a-e) and (N-3)d4T-Trovirdine conjugates (10a-f) were found to be inactive suggesting that the two individual inhibitor compounds do not bind simultaneously in their respective sites.
