Synthesis of furoannelated analogues of Emivirine (MKC-442).
Furoannelated analogues 1-alkoxymethyl-7-phenyl-5, 7-dihydro-1H-furo[3, 4-d]-pyrimidine-2, 4-diones of Emivirine (3a, b) were synthesized from the primary alcohols 1-alkoxymethyl-6-benzyl-5-hydroxymethyl-1H-pyrimidine-2, 4-dione (5a, b) using a radical ring closure reaction with Pb(OAc)(4). These analogues are conformationally restricted in order to fix the aromatic substituent of Emivirine in nearly the same position as it is in the case when the complex of Emivirine is bound to HIV-1 RT. However, the anti HIV-1 activities of 3a, b were considerably lower than those of the lead Emivirine.
Wamberg
Michael
M
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Odense, Denmark.
Pedersen
Erik B
EB
Nielsen
Claus
C
D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; C083858:emivirine