Nonnucleoside HIV-1 reverse-transcriptase inhibitors, part 5. Synthesis and anti-HIV-1 activity of novel 6-naphthylthio HEPT analogues.
As part of a series of studies to discover new HIV reverse-transcriptase inhibitors, various novel 6alpha- and 6beta-naphthylthio 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio) thymine (HEPT) derivatives were synthesized, and in vitro anti-HIV-1 activity was evaluated. The results revealed that most of 6alpha-naphthylthio HEPT derivatives (7a-w) showed good activity [for 7e, IC50 value of 0.048 microM and selectivity index (SI) value of 735; for 7h, IC50 value of 0.057 microM and SI value of 579; for 7k, IC50 value of 0.063 microM and SI value of 565], 6beta-naphthylthio HEPT derivatives (8a-f) showed low activity, but the introduction of alpha nitro group to the C-1 position of the 6beta-naphthyl ring in the 6beta-naphthylthio series (11a-c) resulted in a dramatic increase in anti-HIV-1 activity.
Sun
Guang-Fu
GF
Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
Chen
Xu-Xiang
XX
Chen
Fen-Er
FE
Wang
Yue-Ping
YP
De Clercq
Erik
E
Balzarini
Jan
J
Pannecouque
Christophe
C
D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D013941:Thymine