Synthesis and fluorescent properties of 6-(4-biphenylyl)-3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine analogues of acyclovir and ganciclovir.
Tricyclic (T) analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) carrying the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system [i.e., 6-(4-BrPh)TACV, 5 and 6-(4-BrPh)TGCV, 6] were transformed into 6-[(4'-R2)-4-biphenylyl] derivatives of TACV (7-9) and TGCV (10-12) by Suzuki cross coupling with 4-substituted phenylboronic acids. Compound 11 (R2 = CH2OH) showed a high (approximately 1000) selectivity index against herpes simplex virus type 1 (HSV-1) together with advantageous fluorescence properties (emission in visible region, little overlap with absorption and moderate intensity).
Goslinski
Tomasz
T
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
Wenska
Grazyna
G
Golankiewicz
Bozenna
B
Balzarini
Jan
J
De Clercq
Erik
E
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D007093:Imidazoles; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007093:Imidazoles; D007202:Indicators and Reagents; D015774:Ganciclovir; D000212:Acyclovir