136831-90-8Relevant articles and documents
Synthesis and antiviral activity of N-4'-dihydropyridinyl and dihydroquinolinylcarbonyl-2-hydroxymethyl-5-[cytosin-1'-yl]-1, 3-oxathiolane derivatives against human immunodeficiency virus and duck hepatitis B virus
Camplo,Charvet-Faury,Borel,Turin,Hantz,Trabaud,Niddam,Mourier,Graciet,Chermann,Kraus
, p. 539 - 546 (2007/10/03)
Dihydropyridine and dihydroquinoline derivatives of 2-hydroxymethyl-5-[cytosin-1'-yl]-1,3-oxathiolane ((±)-3TC) have been prepared. The N-4-nicotinate or the N-4-quinoline-carboxylate amides were obtained by reacting nicotinic or quinolinecarboxylic acids with (±)-3TC in the presence of DCC and HOBT. These derivatives were converted into their corresponding N-methylpyridinium and N-methyl quinolinium salts by treatment with MeI in acetone. Reduction of the latter with Na2S2O4 gave dihydropyridine and dihydroquinoline compounds. The N-4-trifluorotoluidinonicotinate derivative was obtained from the coupling of niflumic acid and (±)-3TC using BOP and DIEA. The anti-HIV-1 activities of seven derivatives were determined in MT-4 infected cell cultures. Of these compounds, the IC50 values ranged from 0.1-100 μM, while the IC50 for (±)-3TC was 0.1 μM. The anti-HBV activities were determined in infected duck hepatocytes. Anti-HBV activities of the (±)-3TC derivatives were half that of the parent drug (±)-3TC. The lipophilicity (partition coefficients) of these compounds were determined. The dihydroquinoline prodrugs had greater lipophilicity than the dihydropyridine analogues.
Inhibition of human immunodeficiency virus type 1 replication by phosphonoformate- and phosphonoacetate-2',3'-dideoxy-3'-thiacytidine conjugates
Charvet,Camplo,Faury,Graciet,Mourier,Chermann -,Kraus
, p. 2216 - 2223 (2007/10/02)
The synthesis of potential 'combined prodrugs' where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 μM, while IC50 for BCH-189 in this system was 0.1 μM. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t( 1/2 ) values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti- HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.
In situ complexation directs the stereochemistry of N-glycosylation in the synthesis of oxathiolanyl and dioxolanyl nucleoside analogues
Choi, Woo-Baeg,Wilson, Lawrence J.,Yeola, Suresh,Liotta, Dennis C.,Schinazi, Raymond F.
, p. 9377 - 9379 (2007/10/02)
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