Disease relevance of dioxolane

• BACKGROUND: Amdoxovir (2,6-diaminopurine dioxolane; DAPD) is a nucleoside reverse transcriptase inhibitor (NRTI) of human immunodeficiency virus-1 (HIV-1) with activity against wild-type and NRTI-resistant viruses [1].
• The incorporation of dioxolane analogs into DNA by replicative DNA polymerases could explain their potent cellular toxicity [2].
• The new dioxolane analogue troxacitabine was evaluated in two human pancreatic cancer xenograft models [3].
• In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil [4].
• Absence of mutagenicity of trioxane and dioxolane in Salmonella typhimurium [5].

High impact information on dioxolane

• Amdoxovir ((-)-beta-D-2,6-diaminopurine dioxolane), the prodrug of dioxolane guanosine (DXG), is currently in phase I/II clinical development for the treatment of HIV-1 infection [6].
• Steady-state plasma concentrations of DAPD and dioxolane guanosine followed linear kinetics [7].
• The differential effects of relatively thick monoglyceride bilayers on proton transfer in both dioxolane-linked gA channels must relate to distinct interactions between the bilayers and the SS and RR dioxolanes [8].
• Modulation of proton transfer in the water wire of dioxolane-linked gramicidin channels by lipid membranes [9].
• D- and L-Oxathiolane and -dioxolane derivatives 13, 16, 20, 21, and 29-34 were prepared by glycosylation reaction of the oxathiolane and dioxolane intermediates with silylated uracil analogues using TMSI as the coupling agent [10].

Chemical compound and disease context of dioxolane

• Triangle Pharmaceuticals is developing DAPD, a prodrug of the viral replication inhibitor dioxolane guanosine, as a potential therapy for HIV and HBV infection [11].

Biological context of dioxolane

• Chiral dioxolane inhibitors of leukotriene biosynthesis: structure-activity relationships and syntheses using asymmetric dihydroxylation [12].
• Pharmacokinetics of (-)-beta-D-2-aminopurine dioxolane and (-)-beta-D-2-amino-6-chloropurine dioxolane and their antiviral metabolite (-)-beta-D-dioxolane guanine in rhesus monkeys [13].
• MK-801, (-)-MK-801, and non-competitive NMDA receptor antagonists of the arylcyclohexylamine and dioxolane classes inhibited NMDA stimulated 22Na+ efflux with potencies that reflected their abilities to compete for [3H]MK-801 binding sites in rat cortical membranes [14].
• Studies with the dioxolane (6) yielded no relationship between the lipophilicity of the drug and the efficacy of the enhancer, with an R2 of 0.002 [15].
• Inhalation toxicity of Dioxole and Dioxolane compounds in the rat [16].

Anatomical context of dioxolane

• This study was undertaken to determine dissociation constants (KA and relative efficacies (er) of seven muscarinic agonists (methylfurtrethonium; dioxolane, oxathiolane, carbachol, muscarine, muscarone and oxotremorine) in three isolated tissues (guinea-pig ileum and atria and rat urinary bladder) [17].
• Dioxolane at doses from 1500 mg/kg to 6000 mg/kg caused a significant increase of micronucleated polychromatic erythrocytes in bone marrow of mice as compared to the negative control value [18].

Associations of dioxolane with other chemical compounds

• The new dioxolane, (-)-2'-deoxy-3'-oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts [3].
• Beta-3 adrenoceptor selectivity of the dioxolane dicarboxylate phenethanolamines [19].
• Two chiral columns based on polysaccharide derivatives (Chiralpak AD and Chiralcel OD) have been tested for the chiral separation of several dioxolane compounds, using supercritical fluid chromatography [20].
• Genotoxic effects of dioxolane and trioxane in mice evaluated by the micronucleus test [18].
• Antifungal sordarins. Synthesis and structure-activity relationships of 3',4'-fused dioxolane and dioxane derivatives [21].

Gene context of dioxolane

• The submillisecond closing events (flickers) and the single channel conductances to protons (g(H)) were studied in native gramicidin A (gA) and in the SS and RR diastereoisomers of dioxolane-linked gA channels in planar bilayers [22].
• With the exception of dioxolane, 4-methyldioxolane and 4-ethyldioxolane, these compounds interacted with ferric cytochrome P-450 to give complexes exhibiting type I optical difference spectra, and, after incubation with NADPH, spectra with peaks at about 430 nm [23].
• After preseparation in a C18 and a silica gel column, nineteen pyrone and dioxolane derivatives and two aliphatic esters are obtained, respectively [24].
• Both dioxolane derivatives represent NMDA receptor antagonists, which possess high affinity to the phencyclidine binding site within the NMDA receptor associated ion channel [25].
• The gingkolide terpene, BN 52021 and the dioxolane-based compound BN 52115 had no effect on benzodiazepine binding or chloride channel binding in cortical membrane preparations [26].

Analytical, diagnostic and therapeutic context of dioxolane

• Applications of the Chiralpak AD and Chiralcel OD chiral columns in the enantiomeric separation of several dioxolane compounds by supercritical fluid chromatography [20].

References