Synthesis of 2-(aminocarbonylmethylthio)-1H-imidazoles as novel Capravirine analogues.
Different analogues of Capravirine (AG-1549) or S-1153 were prepared by synthesis of 2-(5-benzyl-4-isopropyl-1-methyl-2,3-dihydro-1H-imidazol-2-ylthio)acetamide (3a-c), ethyl [5-benzyl-1-(ethoxymethyl)-4-ethyl-1H-imidazol-2-ylthio]acetate (10), 2-[5-alkyl-4-substituted 1-(pyridin-4-ylmethyl)-1H-imidazol-2-ylthio]acetamides (12a-f), and 2-[5-benzyl-1-(benzyloxymethyl)-4-isopropyl-1H-imidazol-2-ylthio]acetamides (14a-l) from their corresponding amino acids through a sequence of reactions: Dakin-West reaction, hydrolysis, condensation with thiocyanate derivatives, alkylation with 2-iodoacetamide and ethyl chloroacetate, and coupling with 4-pyridylmethyl chloride, ethoxymethyl chloride and benzyloxymethyl chloride. All the synthesized compounds were screened for their activity against HIV-1 (wild type) and some of them (especially Capravirine like structures) were found active.
Loksha
Yasser M
YM
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
el-Barbary
Ahmed A
AA
el-Badawi
Mahmoud A
MA
Nielsen
Claus
C
Pedersen
Erik B
EB
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D013457:Sulfur Compounds; C433874:capravirine