Improvements in the treatment of tumors in mammals

Claim 2

The use of a compound of formula (I): in which: R 1 is hydrogen, C i -C 4 alkyl or R 2 is a base defined by one of the formulae X is N or C- R 4 ; R 3 is hydrogen, C 1 -C 4 alkyl or R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro or iodo; each R 5 independently is hydrogen or C 1 -C 4 alkyl; or a pharmaceutically-acceptable salt thereof, for the manufacture of a medicament for the treatment of susceptible neoplasms.

Claim 3

The use as claimed in Claim 1 in which the compound of formula (I) is 1-(4-amino-2-oxo-lH-pyrimidin- l-yl)-2-desoxy-2,2-difluororibose, 1-(4-amino-2-oxo-lH-pyrimidin-I-yl)-2-desoxy-2,2-difluoroxylose, 1-(2,4-dioxo-1H,3H-pyrimidin-1-yl)-2-desoxy-2,2-difluororibose, 1-(4-amino-5-methyl-2-oxo-1H-pyrimidin-1-yl)-2-desoxy-2,2-difluororibose, or a pharmaceutically-acceptable salt thereof.

Claim 4

A compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C - R 4 ; R 8 is hydrogen or C i -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N.

Claim 5

A compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C - R 4 ; R 8 is hydrogen or C i -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N.

Claim 6

A compound of formula (II), as defined in claim 3 or a pharmaceutically-acceptable salt thereof for use in the chemotherapy of a mammal.

Claim 7

A compound of formula (II), or a pharmaceutically-acceptable salt thereof for use in the treatment of a susceptible neoplasm in a mammal.

Claim 8

A compound of formula (II), or a pharmaceutically-acceptable salt thereof for use in the treatment of a susceptible neoplasm in a mammal.

Claim 9

A pharmaceutical formulation for use in treating susceptible neoplasms in mammals comprising a compound of Claim 3, or a pharmaceutically-acceptable salt thereof, in combination with a suitable pharmaceutically-acceptable carrier, diluent or excipient therefor.

Claim 10

A compound of formula (III): in which: R 6 is hydrogen or C 1 -C 4 alkyl; and or a pharmaceutically-acceptable salt thereof.

Claim 11

A compound of formula (III): in which: R 6 is hydrogen or C 1 -C 4 alkyl; and or a pharmaceutically-acceptable salt thereof.

Claim 12

A pharmaceutical formulation for use in treating susceptible neoplasms in mammals comprising a compound of Claim 7 in combination with a suitable pharmaceutically acceptable carrier, diluent or excipient therefor.

Claim 13

A compound of formula (III), as defined in claim 7, for use in the chemotherapy of a mammal.

Claim 14

A process for preparing a compound of formula (II) or (III), as defined in Claim 3 or 7, which comprises removing the protecting groups from a correspondingly protected nucleoside of formula (II) or (III).

Claim 15

A process for preparing a compound of formula (II) or (III), as defined in Claim 3 or 7, which comprises: (a) coupling a pyrimidine base of the formula R 7 H, or a protected derivative thereof, with a carbohydrate of formula IV, or a protected derivative thereof: in which the R 7 H pyrimidine base and R 6 are as defined in claim 3 and Leav is a leaving group, and if desired, removing any protecting group present to produce the pyrimidine base product; and (b) if a formula (III) or formula (II) compound in which the base is a purine is desired, reacting with ammonia a corresponding purine nucleoside compound in which a C-2 and/or C-6 substituent of the purine portion of the compound is halogen, and, if desired, alkylating the product.

Claim 16

A process for preparing a compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C-R 4 ; R 8 is hydrogen or C i -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N, which comprises removing the protecting groups from a correspondingly protected nucleoside of formula (II).

Claim 17

A process for preparing a compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C-R 4 ; R 8 is hydrogen or C i -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N, which comprises removing the protecting groups from a correspondingly protected nucleoside of formula (II).

Claim 18

A process for preparing a compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C - R 4 ; R 8 is hydrogen or C 1 -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N which comprises: (a) coupling a pyrimidine base of the formula R 7 H, or a protected derivative thereof, with a carbohydrate of formula IV, or a protected derivative thereof: in which the R 7 H pyrimidine base and R 6 are as defined above and Leav is a leaving group, and if desired, removing any protecting group present to produce the pyrimidine base product; and (b) if a formula (III) or formula (II) compound in which the base is a purine is desired, reacting with ammonia a corresponding purine nucleoside compound in which a C-2 and/or C-6 substituent of the purine portion of the compound is halogen, and, if desired, alkylating the product.

Claim 19

A process for preparing a compound of formula (II): in which: R 6 is hydrogen or C 1 -C 4 alkyl; R 7 is a pyrimidine or purine base of one of the formulae Q is N, C-(C 2 -C 4 alkyl) or C-amino; X is N or C - R 4 ; R 8 is hydrogen or C 1 -C 4 alkyl; R 4 is hydrogen, C 1 -C 4 alkyl, amino, bromo, fluoro, chloro and iodo; or a pharmaceutically-acceptable salt thereof; with the proviso that R 6 and R 8 , both may be hydrogen only when X is N which comprises: (a) coupling a pyrimidine base of the formula R 7 H, or a protected derivative thereof, with a carbohydrate of formula IV, or a protected derivative thereof: in which the R 7 H pyrimidine base and R 6 are as defined above and Leav is a leaving group, and if desired, removing any protecting group present to produce the pyrimidine base product; and (b) if a formula (III) or formula (II) compound in which the base is a purine is desired, reacting with ammonia a corresponding purine nucleoside compound in which a C-2 and/or C-6 substituent of the purine portion of the compound is halogen, and, if desired, alkylating the product.

Claim 20

A process as claimed in Claim 2 for preparing a compound of formula (III): in which: R 6 is hydrogen or C 1 -C 4 alkyl; and a pharmaceutically-acceptable salt thereof.

Claim 21

A process as claimed in any one of Claims 1 to 3 for preparing: 1-(2-chloro-6-amino-9H-purin-9-yl)-2-desoxy-2,2-difluororibose; 1-(2,6-diamino-9H-purin-9-yl)-2-desoxy-2,2-difluororibose; 1-(2,6-dioxo-1H,3H,9H-purin-9-yl)-2-desoxy-2,2-difluororibose; or a pharmaceutically-acceptable salt thereof.

Claim 22

A compound of formula (II) or (III), or a pharmaceutically acceptable salt thereof, whenever prepared according to a process as claimed in any one of claims 1 to 4.