Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles.
A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy.
Merino
I
I
Departamento Química Orgànica y Farmacéutica, Universidad de Navarra, Pamplona, Spain.
Monge
A
A
Font
M
M
Martínez de Irujo
J J
JJ
Alberdi
E
E
Santiago
E
E
Prieto
I
I
Lasarte
J J
JJ
Sarobe
P
P
Borrás
F
F
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors