Synthesis and anti-HIV activity of 2-naphthyl substituted DAPY analogues as non-nucleoside reverse transcriptase inhibitors.
Nine newly 6-cyano-2-naphthyl substituted diarylpyrimidines (DAPY) were synthesized as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. The antiviral and cytotoxicity evaluation indicated that these compounds displayed strong activity against wild-type HIV-1 at nanomolar concentrations with selectivity index SI greater than 23 779. The most active compounds 3c and 3e exhibited activity against the double mutant (103N+181C) strains at an EC₅₀ of 0.16 and 0.15 μM, and were more activity than that of efavirenz.
Liang
Yong-Hong
YH
Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
He
Qiu-Qin
QQ
Zeng
Zhao-Sen
ZS
Liu
Zhi-Qian
ZQ
Feng
Xiao-Qing
XQ
Chen
Fen-Er
FE
Balzarini
Jan
J
Pannecouque
Christophe
C
Clercq
Erik De
ED
D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D048588:Benzoxazines / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
C559228:5-chloro-6-(2-(4-cyanophenylamino)pyrimidin-4-yloxy)-7-methoxy-2-naphthonitrile; C559227:6-(2-(4-cyanophenylamino)pyrimidin-4-yloxy)-5,7-dimethoxy-2-naphthonitrile; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009284:Naphthols; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz