Beta-D-Arabinofuranosylimidazo (4,5-c)pyridine compounds and processes for their production

Claim 2

A compound having the following general formula: or a tautomer thereof, or a pharmaceutically acceptable salt of either thereof, wherein Y is a hydrogen atom or -NH 2 ; X is -NH 2 , -OH or -SH; each of the two radicals R ,which are the same or different, is a hydrogen atom or carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen, a carboxylic acyl radical containing 2 or 3 carbon atoms, or a phosphate group ; with the proviso that, when both X is -OH and Y is -NH 2 , not all of the radicals R and R are hydrogen atoms.

Claim 3

A compound having the following general formula: or a tautomer. thereof, or a pharmaceutically acceptable salt of either thereof, wherein X is -OH or -NH 2 ; each of the two radicals R, which are the same or different, is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms, or a phosphate group: with the proviso that, when X is -OH, not all of the radicals R and R are hydrogen atoms.

Claim 4

A compound having the following general formula: or a tautomer. thereof, or a pharmaceutically acceptable salt of either thereof, wherein X is -OH or -NH 2 ; each of the two radicals R, which are the same or different, is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms, or a phosphate group: with the proviso that, when X is -OH, not all of the radicals R and R are hydrogen atoms.

Claim 5

The compound according to Claim 1 designated 1-β-D-arabinofuranosy-L-1H-imidazo[4,5-c] pyridin-4-amine or a pharmaceutically acceptable salt thereof.

Claim 6

A compound according to Claim 1 and designated 1-β-D-arabinfuranosyl-1H-imidazo [4, 5-c]pyridin-4-amine 5'-phosphate; 1-β-D-arabinofuranosyl-1,5-dihydro-4H-imidazo[4,5-c]-pyridin-4-one; 1-β-D-arabinofuranosyl-1,5-dihydrO-4H-imidazo[4,5-c]-pyridin-4-one 5'-phosphate; 1-β-D-arabinofuranosyl-1,5-dihydro-4H-imidazo[4, 5-c]-pyridine-4-thione; 1-(2,3,5,-tri-0-acetyl-β-D-arabinofuranosyl-1H-imidazo-[4, 5-c] pyridin-4-amine; 6-amino-1-β-D-arabinofuranosyl-1,5-dihydro-4H-imidazo-[4, 5-c] pyridin-4-one 5'-phosphate; 1-β-D-arabinofuranosyl-4,6-diamino-1H-imidazo[4, 5-c] - pyridine; 1-β-D-arabinofuranosyl-4,6-diamino- 1H-imidazo[4,5-c] - pyridine 5'-phosphate; or 6-amino-1-β-D-arabinofuranosyl-1,5-dihydro-4H-imidazo-[4,5-c]pyridine-4-thione; or a pharmaceutically acceptable salt of any thereof.

Claim 7

A compound according to Claim 2 and designated 6-amino-3-β-D-arabinofuranosyl-3,5-dihydro-4H-imidazo-[4,5-c]pyridin-4-one 5'-phosphate; 3-β-D-arabinofuranosyl-4,6-diamino-3H-imidazo[4,5-c]-pyridine; or 3-β-D-arabinofuranosyl-4,6-diamino-3H-imidazo[4,5-c]-pyridine 5'-phosphate; or a pharmaceutically acceptable salt of any thereof.

Claim 8

A process for producing a compound of the following general formula : or a tautomer thereof, wherein X is -NH 2 , -OH or -SH;R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms, or a phosphate group; which process comprises β-D-arabinofuranosylating 4-chloro-lH-imidazo-[4,5-c] pyridine with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; treating the resulting blocked nucleoside sequentially with hydrazine, Raney nickel and sodium in liquid ammonia to obtain 1-β-D-arabinofuranosyl-1H-imidazo[4,5-c]pyridin-4-amine, and optionally acylating and/or phosphorylating and/or converting the 4-amino group to a -OH or -SH group to obtain the desired compound wherein the 4-chloro-1H-imidazo[4, 5-c] pyridine is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabinofurasylated with the: 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 9

A process for producing a compound of the following general formula : or a tautomer thereof, wherein X is -NH 2 , -OH or -SH;R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms, or a phosphate group; which process comprises β-D-arabinofuranosylating 4-chloro-lH-imidazo-[4,5-c] pyridine with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; treating the resulting blocked nucleoside sequentially with hydrazine, Raney nickel and sodium in liquid ammonia to obtain 1-β-D-arabinofuranosyl-1H-imidazo[4,5-c]pyridin-4-amine, and optionally acylating and/or phosphorylating and/or converting the 4-amino group to a -OH or -SH group to obtain the desired compound wherein the 4-chloro-1H-imidazo[4, 5-c] pyridine is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabinofurasylated with the: 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 10

A process for producing a compound of the following general formula :- or a tautomer thereof, wherein R is a hydrogen atom or a carboxylic radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group, with the proviso that not all of R and R 1 are hydrogen atoms.; which process comprises β-D-arabinofuranosylating methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; separating and collecting the β-anomers ; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 6-amino-1,5-dihydro-1-β-D-arabinofuranosyl-4H-imidazo[4,a-c]pyridin-4-one; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compounds.; wherein the methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabinofuranosylated with the 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 11

A process for producing a compound of the following general formula :- or a tautomer thereof, wherein R is a hydrogen atom or a carboxylic radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group, with the proviso that not all of R and R 1 are hydrogen atoms.; which process comprises β-D-arabinofuranosylating methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; separating and collecting the β-anomers ; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 6-amino-1,5-dihydro-1-β-D-arabinofuranosyl-4H-imidazo[4,a-c]pyridin-4-one; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compounds.; wherein the methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabinofuranosylated with the 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 12

A process for producing a compound of the following general formula:- or a tautomer thereof, wherein R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group, with the proviso that not all of R and R 1 are hydrogen atoms; which process comprises β-D-arabinofuranosylating methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; separating and collecting the β-anomers; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 6-amino-3-β-D-arabinofuranosyl-3,5-dihydro-4H-imidazo [4, 5-c] pyridin-4-one; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound; wherein the methyl 4(5)-cyanomeahylimidazole-5(4)-carboxylate is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabfnofuranosylated with the. 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 13

A process for producing a compound of the following general formula:- or a tautomer thereof, wherein R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group, with the proviso that not all of R and R 1 are hydrogen atoms; which process comprises β-D-arabinofuranosylating methyl 4(5)-cyanomethylimidazole-5(4)-carboxylate with 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride; separating and collecting the β-anomers; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 6-amino-3-β-D-arabinofuranosyl-3,5-dihydro-4H-imidazo [4, 5-c] pyridin-4-one; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound; wherein the methyl 4(5)-cyanomeahylimidazole-5(4)-carboxylate is treated with sodium hydride in a suitable solvent to form the anion having the formula which anion is β-D-arabfnofuranosylated with the. 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 14

A process for producing a compound of the following general formula:- or-a tautomer thereof, wherein R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group; which process compris.es β-D-arabinofuranosylating 4(5)-cyano-5(4)-cyanomethylimidazole with 2,3,5,-tri-0-benzyl-a-D-arabinofuranosyl chloride; separating and collecting the β-anomers ; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 1-β-D-arabinofuranosyl-4,6-diamino-1H-imidazo[4,5-c]pyridine; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound; wherein the 4(5)-cyano-5(4)-cyanomethylimidazole is treated with sodium hydride in a suitable solvent to form the anion having the formula:- which anion is β-D-arabinofuranosylated with the 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 15

A process for producing a compound of the following general formula:- or-a tautomer thereof, wherein R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acyl radical containing 2 or 3 carbon atoms or a phosphate group; which process compris.es β-D-arabinofuranosylating 4(5)-cyano-5(4)-cyanomethylimidazole with 2,3,5,-tri-0-benzyl-a-D-arabinofuranosyl chloride; separating and collecting the β-anomers ; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 1-β-D-arabinofuranosyl-4,6-diamino-1H-imidazo[4,5-c]pyridine; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound; wherein the 4(5)-cyano-5(4)-cyanomethylimidazole is treated with sodium hydride in a suitable solvent to form the anion having the formula:- which anion is β-D-arabinofuranosylated with the 2,3,5-tri-0-benzyl-α-D-arabinofuranosyl chloride.

Claim 16

A process for producing a compound of the following general formula:- or a tautomer thereof, where.in R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acid radical containing 2 or 3 carbon atoms or a phosphate group; which process comprises β-D-arabinofuranosylating 4(5)-cyano-5 (4)-cyanomethylimidazole with 2,3,5-tri-0-benzyl-a-D-arabinofuranosyl chloride; separating and collecting the β-anomers; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 3-β-D-arabinofuranosyl-4,6-diamino-3H-imidazo 4,5-c pyridine; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound, wherein the 4(5)-cyano-5(4)-cyanomethylimidazole is treated with sodium hydride in a suitable solvent to form the anion having the formula :- which anion is β-D-arabinofuranosylated with the 2, 3, 5-tri-O-benzyl-α-D-arabinofuranosyl chloride.

Claim 17

A process for producing a compound of the following general formula:- or a tautomer thereof, where.in R is a hydrogen atom or a carboxylic acyl radical containing 2 or 3 carbon atoms; and R 1 is a hydrogen atom, a carboxylic acid radical containing 2 or 3 carbon atoms or a phosphate group; which process comprises β-D-arabinofuranosylating 4(5)-cyano-5 (4)-cyanomethylimidazole with 2,3,5-tri-0-benzyl-a-D-arabinofuranosyl chloride; separating and collecting the β-anomers; treating the resulting blocked nucleoside with sodium in liquid ammonia to obtain 3-β-D-arabinofuranosyl-4,6-diamino-3H-imidazo 4,5-c pyridine; and acylating and/or phosphorylating the last mentioned compound to obtain the desired compound, wherein the 4(5)-cyano-5(4)-cyanomethylimidazole is treated with sodium hydride in a suitable solvent to form the anion having the formula :- which anion is β-D-arabinofuranosylated with the 2, 3, 5-tri-O-benzyl-α-D-arabinofuranosyl chloride.