Synthesis and anti-HIV activity of [d4U]-[trovirdine analogue] and [d4T]-[trovirdine analogue] heterodimers as inhibitors of HIV-1 reverse transcriptase.
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.
Gavriliu
D
D
Centre d'Etudes et de Recherche sur le Médicament de Normandie, U.F.R. des Sciences Pharmaceutiques, 5 Rue Vaubénard, 14032 Caen, France.
Fossey
C
C
Ciurea
A
A
Delbederi
Z
Z
Sugeac
E
E
Ladurée
D
D
Schmidt
S
S
Laumond
G
G
Aubertin
A M
AM
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019281:Dimerization; D004353:Drug Evaluation, Preclinical; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000821:virology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018119:Stavudine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; C058925:2',3'-didehydro-2',3'-dideoxyuridine; D018119:Stavudine; D054303:HIV Reverse Transcriptase; C095511:trovirdine