New acyclic quinoxaline nucleosides. Synthesis and anti-hiv activity.
A series of acyclonucleosides substituted 1-(4,5-dihydroxypentyl) (13-8) and 2-(4,5-dihydroxypentyloxy)quinoxalines (19-24) were synthesized by the sharpless asymmetric dihydroxylation of the derivatives 1-6 and 7-12, respectively. Treatment of the quinoxaline base 26 with (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl-p-toluenesulfonate (27) in the presence of NaH/DMF furnished 28. Acid hydrolysis of 28 gave 1-(2,3-dihydroxypropyl)-6,7-dimethyl-quinoxaline-2-one (29). Alternatively, 29 was prepared by sharpless dihydroxylation of 30. All the compounds were evaluated for their in vitro anti-HIV-1 and HIV-2 in MT-4 cell and found inactive, except 29, which showed inhibition of HIV-1 with EC50 value of 0.15 +/- 0.1 microg/ml and a therapeutic index (SI) of 73.
Ali
Ibrahim A I
IA
Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt.
Al-Masoudi
Iman A
IA
Aziz
Nazik M
NM
Al-Masoudi
Najim A
NA
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D009705:Nucleosides; D011810:Quinoxalines