Therapeutic nucleosides

Claim 2

A compound of formula (1): or a pharmaceutically acceptable derivative thereof, for use in therapy, provided that when the 3'-azido group of formula (I) is in the eryhro configuration, the said compound is not for use in the treatment or prophylaxis of human retrovirus infections.

Claim 3

A compound of formula (I) as claimed in claim 1 wherein the 3'-azido group is in the threo configuration, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of human retrovirus infections.

Claim 4

The compound of formula (I) claimed in claim 2, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of HTLV-I or HTLV-II infections.

Claim 5

The compound of formula (I) as claimed in claim 2, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of AIDS.

Claim 6

The compound of formula (I) as claimed in claim 2, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of an AIDV infection.

Claim 7

A compound of formula (I) as claimed in claim 1, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of non- human animal retrovirus infections.

Claim 8

A compound of formula (I) as claimed in claim 1, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of a feline leukaemia virus or equine infectious anaemia virus infection.

Claim 9

A compound of formula (I) as claimed in claim 1, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of a gram-negative bacterial infection.

Claim 10

A compound of formula (I) as claimed in claim 1, or a pharmaceutically acceptable derivative thereof, for use in the treatment or prophylaxis of calf neonatal enteritis, pig post-weaning enteritis or chicken colisepticaemia.

Claim 11

A pharmaceutically acceptable derivative in the form of a salt, ester or salt of said ester of a compound of formula (I) for use as claimed in any of the preceding claims.

Claim 12

Use of a compound of formula (I) (as defined in claim 1), or a pharmaceutically acceptable derivative thereof, in the manufacture of a medicament for the treatment or prophylaxis of retrovirus infections, provided that when the 3'-azido group of formula (I) is in the er y thro configuration, the said medicament is not for the treatment or prophylaxis of human retrovirus infections.

Claim 13

Use of a compound of formula (I), or a pharmaceutically acceptable derivative thereof, as claimed in claim 11, wherein the 3'-azido group is in the three configuration and the said medicament is for the treatment or prophylaxis of a human retrovirus infection.

Claim 14

Use of a compound of formula (I), or a pharmaceutically acceptable derivative thereof, as claimed in claim 12, wherein the said medicament is for the treatment of prophylaxis of HTLV-I or HTLV-II infections.

Claim 15

Use of a compound of formula (I), or a pharmaceutically acceptable derivative thereof, as claimed in claim 12, wherein the said medicament is for the treatment or prophylaxis of AIDS.

Claim 16

Use of a compound of formula (I), or a pharmaceutically acceptable derivative thereof, as claimed in claim 12, wherein the said medicament is for the treatment or prophylaxis of an AIDV infection.

Claim 17

Use of a compound of formula (I), or a pharmaceutically acceptable derivative thereof, as claimed in claim 11, wherein the said medicament is for treatment or prophylaxis as defined in any of claims 6 to 10.

Claim 18

Use of a pharmaceutically acceptable salt, ester or salt of said ester of a compound of formula - (I) as claimed in any of claims 11 to 16.

Claim 19

A pharmaceutical formulation comprising as active ingredient, 1-(3'-azido-2',3'-dideoxy-β-D-threo -pentofuranosyl)thymine or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier therefor.

Claim 20

A pharmaceutical formulation comprising as active ingredient, 1-(3'-azido-2',3'-dideoxy-β-D-threo -pentofuranosyl)thymine or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier therefor.

Claim 21

A formulation as claimed in claim 18 which is sterile.

Claim 22

A formulation as claimed in claim 19 adapted for administration by injection.

Claim 23

A formulation as claimed in claim 18 for oral administration.

Claim 24

A formulation according to claim 21 in the form of a tablet or capsule.

Claim 25

A process for the preparation of a formulation according to any of claims 18 to 22 which comprises bringing the said active ingredient into association with the said pharmaceutically acceptable carrier.

Claim 26

Pharmaceutically acceptable salts and esters of 1-(3'-azido-2',3'-dideoxy-,6-D-threo-pentofuranosyl)-thymine.

Claim 27

Pharmaceutically acceptable salts and esters of 1-(3'-azido-2',3'-dideoxy-,6-D-threo-pentofuranosyl)-thymine.

Claim 28

The phenoxyacetate and methoxyacetate esters of 1-(3'-azido-2',3'-dideoxy-,6-D-t hreo-pentofuranosyl)thymine. Claims for contracting state: AT

Claim 29

A process for the preparation of a pharmaceutical formulation comprising bringing 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosy)thymine, or a pharmaceutically acceptable derivative thereof, as active ingredient, into association with a pharmaceutically acceptable carrier therefor.

Claim 30

A process for the preparation of a pharmaceutical formulation comprising bringing 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosy)thymine, or a pharmaceutically acceptable derivative thereof, as active ingredient, into association with a pharmaceutically acceptable carrier therefor.

Claim 31

A process for the preparation of a formulation according to claim 1 wherein the ingredients are sterile.

Claim 32

A process for the preparation of a formulation according to claim 2 wherein the said formulation is adapted for administration by injection.

Claim 33

A process for the preparation of a formulation according to claim 1 wherein the said formulation is further adapted for oral administration.

Claim 34

A process for the preparation of a formulation according to claims 1 or 4 wherein the said formulation is made in the form of a tablet or capsule.

Claim 35

A process for the preparation of a formulation according to claims 1 or 2 wherein the said formulation is further adapted to provide sustained release of the active ingredient after oral administration.

Claim 36

A process for the preparation of a formulation according to any of claims 1 to 6 wherein the active ingredient is 1-(3'-azido-2',3'-dideoxy-,B-Q-threo-pentofuranosyf)thymine.

Claim 37

A process for the preparation of a pharmaceutically acceptable derivative of 1-(3'-azido-2',3'- dideoxy-β-D-threo-pentofuranosyl)thymine, which derivative is, upon administration to an animal subject, capable of providing (directly or indirectly) 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)-thymine, or a therapeutically active metabolite or residue thereof, said process comprising either (A) reacting a compound of formula: (wherein M represents a precursor group for the 3'-azido group) or a derivative (e.g. an ester or salt) thereof, with an agent or under conditions serving to convert the said precursor group into the desired azido group; or (B) reacting a compound of formula: (wherein R represents a precursor group for the hydroxy group, or for a pharmaceutically acceptable derivative group thereof) with an agent or under conditions serving to convert the said precursor group into the corresponding desired group: or (C) reacting a compound of formula or a functional equivalent thereof, with a compound serving to introduce the desired ribofuranosyl ring at the 1-position of the compound of formula (IV); or (D) reacting a compound of formula (wherein R' is hydroxy or R as defined above), with an agent under conditions serving to convert the said compound into 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)thymine, or a pharmaceutically acceptable derivative thereof; and (i) when 1-(3'-azido-2',3'-dideoxy-β-D-threo pentofuranosyl)thymine is formed, converting the said compound into a pharmaceutically acceptable derivative thereof, or (ii) when a pharmaceutically acceptable derivative of 1-(3'-azido-2',3'-dideoxy-β-D-threo- pentofuranosyl)thymine is formed, optionally converting the said derivative simultaneously or thereafter into 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)thymine, or a different derivative thereof.

Claim 38

A process for the preparation of a pharmaceutically acceptable derivative of 1-(3'-azido-2',3'- dideoxy-β-D-threo-pentofuranosyl)thymine, which derivative is, upon administration to an animal subject, capable of providing (directly or indirectly) 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)-thymine, or a therapeutically active metabolite or residue thereof, said process comprising either (A) reacting a compound of formula: (wherein M represents a precursor group for the 3'-azido group) or a derivative (e.g. an ester or salt) thereof, with an agent or under conditions serving to convert the said precursor group into the desired azido group; or (B) reacting a compound of formula: (wherein R represents a precursor group for the hydroxy group, or for a pharmaceutically acceptable derivative group thereof) with an agent or under conditions serving to convert the said precursor group into the corresponding desired group: or (C) reacting a compound of formula or a functional equivalent thereof, with a compound serving to introduce the desired ribofuranosyl ring at the 1-position of the compound of formula (IV); or (D) reacting a compound of formula (wherein R' is hydroxy or R as defined above), with an agent under conditions serving to convert the said compound into 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)thymine, or a pharmaceutically acceptable derivative thereof; and (i) when 1-(3'-azido-2',3'-dideoxy-β-D-threo pentofuranosyl)thymine is formed, converting the said compound into a pharmaceutically acceptable derivative thereof, or (ii) when a pharmaceutically acceptable derivative of 1-(3'-azido-2',3'-dideoxy-β-D-threo- pentofuranosyl)thymine is formed, optionally converting the said derivative simultaneously or thereafter into 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)thymine, or a different derivative thereof.

Claim 39

A process for the preparation of a pharmaceutically acceptable derivative of 1-(3'- azido-2',3'dideoxy-β-D-threo -pentofuranosyl)-thymine, according to claim 8 when the said derivative is a pharmaceutically acceptable salt, ester or salt of such ester of 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)-thymine.

Claim 40

A process for the preparation of a pharmaceutically acceptable derivative of 1-(3'- azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)-thymine, according to claim 8 when the said derivative is either the phenoxyacetate or the methoxyacetate ester.

Claim 41

A process for the preparation of a formulation according to any of claims 1 to 7 comprising the steps of: (A) preparing 1-(3'-azido-2',3'-dideoxy-,8-D-threo- pentofuranosyl)thymine, or a pharmaceutically acceptable derivative thereof, by either (i) reacting a compound of formula (wherein M represents a precursor group for the 3'-azido group) or a derivative (e.g. an ester or salt) thereof, with an agent or under conditions serving to convert the said precursor group into the desired azido group: or (ii) reacting a compound of formula: (wherein R represents a precursor group for the hydroxy group, or for a pharmaceutically acceptable derivative group thereof) with an agent or under conditions serving to convert the said precursor group into the corresponding desired group; or (iii) reacting a compound of formula or a functional equivalent thereof, with a compound serving to introduce the desired ribofuranosyl ring at the 1-position of the compound of formula (IV); or (iv) reacting a compound of formula (wherein R' is hydroxy or R as defined above), with an agent or under conditions serving to convert the said compound into 1-(3'-azido-2',3'-dideoxy-β-D-threo-pentofuranosyl)-thymine, or a pharmaceutically acceptable derivative thereof; and thereafter, or simultaneously therewith, effecting one or more of the following optional conversions: (i) when 1-(3'-azido-2',3'-dideoxy-β-D-threo -pentofuranosyl)thymine is formed, converting the said compound into a pharmaceutically acceptable derivative thereof, (ii) when a pharmaceutically acceptable derivative of 1-(3'-azido-2',3'-dideaxy-β-D-threo-pentofuranosyl)thymine is formed, converting the said derivative into 1-{3'- azido-2',3'-dideoxy-β-D -threo-pen- tofuranosyl)thymine, or a different derivative thereof; and (B) bringing the product of process (A) into association with the said pharmaceutically acceptable carrier therefor.