Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het=2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.
Thakur
Vinay V
VV
Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
Kim
Joseph T
JT
Hamilton
Andrew D
AD
Bailey
Christopher M
CM
Domaoal
Robert A
RA
Wang
Ligong
L
Anderson
Karen S
KS
Jorgensen
William L
WL
D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000201:enzymology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
D000588:Amines; D011743:Pyrimidines; D014227:Triazines; D054303:HIV Reverse Transcriptase