5-Substituted 1-(2'-deoxy-2'-substituted-beta-D-arabinofuranosyl) pyrimidine nucleosides and pharmaceutical compositions containing them

Claim 2

Pyrimidine nucleosides having the formula wherein A is O R 3 , S R 3 , NR 3 R 4 or NHacyl wherein R 3 and R 4 are the same or different and are hydrogen, lower alkyl of 1 to 7 carbon atoms, aralkyl, or aryl; NHacyl is alkanoyl or aroyl amide; B is oxygen or sulfur; X is halogen, alkylsulfonyl or arylsulfonyl; Y is halogen, amino, monoalkyl- or monoaralkylamino, dialkylamino, aminomethyl, hydroxymethyl, lower alkyl, aryl, aralkyl, vinyl and substituted vinyl or ethynyl and substituted ethynyl; Z is methyne or nitrogen; R 1 and R 2 are the same or different and are hydrogen acyl or aroyl.

Claim 3

Nucleosides of Cl 1 selected from the group of 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)- 5-methylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-I 5-ethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-vinylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethynylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylaminocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminomethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-hydroxymethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl) 5-fluorocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl) 5-chlorocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-fluorocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine. 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine.

Claim 4

Nucleosides of Cl 1 selected from the group of 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)- 5-methylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-I 5-ethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-vinylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethynylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylaminocytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminomethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-hydroxymethylcytosine, 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl) 5-fluorocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl) 5-chlorocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine, 1-(3,5-di-0-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-fluorocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine. 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-iodocytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine, 1-(3,5-di-0-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine.

Claim 5

Nucleosides of Cl 1 selected from the group of 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-B-B-arabinofuranosyl)-5-fluorouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-6-azathymine, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-fluorouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deaxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-thymine, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-6-azathymine, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-fluorouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-thymine, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-6-azathymine.

Claim 6

Nucleosides of Cl 1 selected from the group of 1-(3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-B-B-arabinofuranosyl)-5-fluorouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil, 1-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-6-azathymine, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-fluorouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deaxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-thymine, 1-(3,5-di-O-acetyl-2-chloro-2-deoxy-β-D-arabinofuranosyl)-6-azathymine, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-fluorouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-thymine, 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-arabinofuranosyl)-6-azathymine.

Claim 7

Nucleosides of Cl 1 selected from the group of 1-(2-deoxy-2-fluoro-S-D-drabinofuranosyl)-5-bromocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorocytosine, ; 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-fluorocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methylcytosine.

Claim 8

Nucleosides of Cl 1 selected from the group of 1-(2-deoxy-2-fluoro-S-D-drabinofuranosyl)-5-bromocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-chlorocytosine, ; 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-fluorocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methylcytosine.

Claim 9

Nucleosides of Cl 1 selected from the group of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-S-vinylcytosine, 1-(2-deoxy-2-fluoro-S-D-arabinofuranosyl)-5-ethynylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylaminocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminomethylcytosine, 1-(2-deoxy-2-fluoro-S-D-arabinofuranosyl)-5-hydroxymethylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(2-chloro-2-deohy-β-D-arabinofuranosyl)-5-fluorocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arab inofuranosyl)-5-iodocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine hydrochloride 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine hydrochloride, 1-(2-bromo-2-debxy-β-D-arabinofuranosyl)-5-fluorocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-S-iodocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine hydrochloride, and 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine hydrochloride.

Claim 10

Nucleosides of Cl 1 selected from the group of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-S-vinylcytosine, 1-(2-deoxy-2-fluoro-S-D-arabinofuranosyl)-5-ethynylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-benzylaminocytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-aminomethylcytosine, 1-(2-deoxy-2-fluoro-S-D-arabinofuranosyl)-5-hydroxymethylcytosine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methyl-6-azacytosine, 1-(2-chloro-2-deohy-β-D-arabinofuranosyl)-5-fluorocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arab inofuranosyl)-5-iodocytosine hydrochloride, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine hydrochloride 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine hydrochloride, 1-(2-bromo-2-debxy-β-D-arabinofuranosyl)-5-fluorocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-bromocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-S-iodocytosine hydrochloride, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methylcytosine hydrochloride, and 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-methyl-6-azacytosine hydrochloride.

Claim 11

Nucleosides of claim 1 selected from the group of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-fluorouracil, 1-(2-deoxy-2-fluoro-B-D-arabinofuranosyl)-5-chlorouracil, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-bromouracil and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil.

Claim 12

Nucleosides of claim 1 selected from the group of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-6-azathymine, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-fluorouracil, 1-(2-chloro-2-deoxy-B-D-arabinofuranosyl)-5-chlorouracil, 1-(2-chlaro-2-deoxy-β-D-arabinofuranosyl)-5-bromouracil, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)thymine, 1-(2-chloro-2-deoxy-β-D-arabinofuranosyl)-6-azathymine, 1-(2-bromo-2-deoxy-S-D-arabinofuranosyl)-5-fluorouracil, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-chlorouracil, 1-(2-bromo-2-deoxy-β-D-arabin6furanosyl)-5-bromouracil, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)-5-iodouracil, 1-(2-bromo-2-deoxy-β-D-arabinofuranosyl)thymine and 1-(2-bromo-2-deoxy-R-D-arabinofuranosyl)-6-azathymine.

Claim 13

Pharmaceutical composition comprising an effective amount of a nucleoside of the formula defined in claim 1 or of a pharmaceutically acceptable acid addition salt thereof together with a pharmaceutically acceptable carrier.

Claim 14

Method of producing an anti-viral effect in a warm-blooded animal which comprises administering to said anima an effective amount of a nucleoside of the formula defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof.

Claim 15

lo. Method of producing anti-tumor effect in a warm-blooded animal which comprises administering to said animal an effective amount of a nucleoside of the formula defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof.