Biaryl acids: novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2.
A series of biaryl acids has been found to show micromolar inhibition of the HIV reverse transcriptase (RT) from types 1 and 2 with IC50S in the micromolar range. The series was discovered by consideration of the polymerase active site and sub-structure searching of the company compound collection. Synthesis of analogues to investigate the SAR is described. Two of these compounds have shown inhibition of HIV-2 RT only.
Milton
J
J
Department of Chemistry, GlaxoWellcome Medicines Research Center, Stevenage, Oxford.
Slater
M J
MJ
Bird
A J
AJ
Spinks
D
D
Scott
G
G
Price
C E
CE
Downing
S
S
Green
D V
DV
Madar
S
S
Bethell
R
R
Stammers
D K
DK
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D002264:Carboxylic Acids; D006841:Hydrocarbons, Aromatic; D018894:Reverse Transcriptase Inhibitors; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase