RESUMEN
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.
Asunto(s)
Alquinos/química , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacología , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/farmacología , Estavudina , Fármacos Anti-VIH/química , Línea Celular , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Inhibidores de la Transcriptasa Inversa/química , Estavudina/análogos & derivados , Estavudina/síntesis química , Estavudina/farmacología , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
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.
Asunto(s)
VIH-1/fisiología , Inhibidores de la Transcriptasa Inversa/síntesis química , Replicación Viral/efectos de los fármacos , Dimerización , VIH-1/efectos de los fármacos , Indicadores y Reactivos , Modelos Moleculares , Estructura Molecular , Piridinas/química , Inhibidores de la Transcriptasa Inversa/farmacologíaRESUMEN
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.