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K W Pankiewicz

Publications and source records attributed to K W Pankiewicz.

29 records · Page 2Linked to original sources
PubMed1987

Synthesis of 5-beta-D-ribofuranosylnicotinamide and its N-methyl derivative. The isosteric and isoelectronic analogues of nicotinamide nucleoside.

The pyridine C-nucleosides 5-beta-D-ribofuranosylnicotinamide and its N-methylpyridinium derivative (1 and 2), which are isosteric and isoelectronic, respectively, to nicotinamide nucleoside were synthesized. Condensation of 3-bromo-5-lithiopyridine with 2,4:3,5-di-O-benzylidene-D-aldehydoribose (7) afforded an allo/altro mixture of the corresponding bromopyridine derivatives, which were converted into nicotinamide C-nucleoside precursors 10. Mesylation of the hydroxyl group of 10 followed by acid hydrolysis of the product afforded the anomeric nicotinamide C-nucleosides. The beta anomer 1 was separated and treated with MeI to give 2.

NAD↗
PubMed1987

Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6.

The synthesis of 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-O-acetyl-2'-O-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur (1+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-O-acetyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1- methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.

Animals↗
PubMed1987

Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides.

Synthesis of the C-nucleoside, 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil, isosteric to the potent antiviral and anticancer nucleoside, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (2'-fluoro-5-methyl-ara-U or FMAU) was achieved by exploitation of the 4,5'-anhydro-nucleoside. Attempts at application of this ribosyl-to-arabinosyl pyrimidine transformation to 2,5'-anhydrouridine resulted in the formation of 2,2'-anhydro-5-substituted-arabinosyluracil.

Arabinonucleosides↗
PubMed1982

Nucleosides. 125. Synthesis of 5'-deoxy-5'-substituted-1,3-dimethyl-psi-uridines from 3',5'-O-(1,1,3,3-tetraisopropyldisiloxanyl)-1,3-dimethyl-psi-uridine. A novel isomerization reaction.

Treatment of 3'-5'-O-(1,1,3,3-tetraisopropyldisiloxanyl)-1,3-dimethyl-psi-uridine (7) . with one equivalent of base and a slight excess of trifluoromethanesulfonic anhydride afforded 5'-O-trifluoromethanesulfonyl-2',3'-O-(1, 1,3,3-tetraisopropyldisiloxanyl)-1,3-dimethyl-psi-uridine (8). Nucleophilic displacement of the 5'-trifluoromethanesulfonyloxy group by treatment with various alkali metal salts of halide, azide, or acetate followed by deprotection by fluoride ion treatment afforded the corresponding 5'-substituted-1, 3-dimethyl-psi-uridine derivatives (10) in good yields in crystalline form.

Crystallization↗
PubMedDate not supplied

Novel nicotinamide adenine dinucleotide analogues as potential anticancer agents: quest for specific inhibition of inosine monophosphate dehydrogenase.

Synthetic nicotinamide adenine dinucleotide (NAD) analogues containing 5-beta-D-ribofuranosylnicotinamide (C-NAD), 6-beta-D-ribofuranosylpicolinamide (C-PAD), 3-beta-D-ribofuranosylbenzamide (BAD), and 2-beta-D-ribofuranosylthiazole-4-carboxamide (TAD) in place of the nicotinamide riboside moiety are described and evaluated as potential inhibitors of inosine monophosphate dehydrogenase (IMPDH). TAD and BAD showed potent inhibitory activity against the enzyme in the form of pyrophosphates, as well as metabolically stable methylene- and difluoromethylenebis(phosphonate)s. Fluorination at the C2' (ribo and arabino configuration) and C3' (ribo) of the adenosine moiety of TAD afforded analogues highly potent against IMPDH, but weakly active against alcohol dehydrogenase. With the exception of the methylenebis(phosphonate) analogue of TAD compounds containing a methylene bridge were poor inhibitors of growth of K562 cells. On the other hand, NAD analogues containing difluoromethylene linkage were highly effective in inhibition of K562 cell growth, as well as potent inducers of K562 cell differentiation. Such compounds, therefore, may be of potential therapeutic interest.

Animals↗
PubMedDate not supplied

Novel mycophenolic adenine bis(phosphonate)s as potent anticancer agents and inducers of cells differentiation.

An effective treatment of myeloid leukemias would rely on inducing myeloid cells to undergo differentiation. It has been demonstrated that inhibition of IMPDH with mycophenolic acid or tiazofurin resulted in inhibition of cell growth as well as induction of differentiation. We synthesized a number of bis(phosphonate) analogues of tiazofurin-, benzamide-, and mycophenolic-adenine dinucleotide which were found to be cytotoxic as well as effective inducers of cell differentiation.

Adenine Nucleotides↗