Synthesis and anti-HIV activity of some heterodimers [NRTI]-glycyl-succinyl-[trovirdine analogue] of known HIV-1 reverse transcriptase inhibitors.
Expected for their ability to inhibit HIV replication, four heterodimers with a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) bound by a linker arm were designed and synthesized. For the NRTIs, d4U, d2U, d4T and 5'-O-acetyl-5-(3-hydroxypropynyl)d2U were chosen. For the NNRTI, a Trovirdine Analogue (belonging to the phenethylthiazolylthiourea class) was chosen. The conjugation of the two different inhibitors (NRTI and NNRTI) was performed using the succinyl-glycine moiety as a spontaneously cleavable linker.
Sugeac
Elena
E
Centre d'Etudes et de Recherche sur le Médicament de Normandie, U.F.R. des Sciences, Pharmaceutiques, 5, Rue Vaubénard, F-14032, Caen Cedex, France.
Fossey
Christine
C
Ladurée
Daniel
D
Schmidt
Sylvie
S
Laumond
Geraldine
G
Aubertin
Anne-Marie
AM
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D019281:Dimerization; D005998:Glycine / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019802:Succinic Acid / Q000737:chemistry
D019380:Anti-HIV Agents; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019802:Succinic Acid; D054303:HIV Reverse Transcriptase; D005998:Glycine; C095511:trovirdine